Twins vs. Red Sox Prediction, MLB Picks for Friday, May 22

The Minnesota Twins (23-27) and the Boston Red Sox (22-27) are set to begin a three-game series on Friday, May 22, at 7:10 p.m. ET.

Before the start of Friday’s showdown, the Red Sox are home favorites with a 1.61x payout if they defeat the Twins, via PrizePicks Team Picks.

Below, we'll break down our Twins vs. Red Sox prediction and picks for Friday’s MLB contest, including the run line, over/under, and key player picks for PrizePicks.

Make your Twins vs. Red Sox prediction on PrizePicks for tonight's game.

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Twins vs. Red Sox Prediction, Winner Payout, Over/Under – Friday, May 22

To get this series underway, it will be the Twins SP Connor Prielipp (3.84 xFIP across 5 starts and 25 IP in 2026) and the Red Sox SP Payton Tolle (3.81 xFIP across 5 starts and 30.2 IP) facing off on the bump.

Prielipp has been extremely solid since joining Minnesota’s rotation, ranking in the 80th percentile in xERA (3.07) and 92nd percentile in xBA (.185), via Baseball Savant. 

The left-handed starter has flashed upside as the Twins’ No. 5-ranked prospect, but his 15th percentile barrel rate (11.5%) and 30th percentile groundball rate (38.7%) have led to permitting at least 1 homer in three straight starts.

Outside of OF Byron Buxton, the Twins’ lineup has been inconsistent, generating the 15th-best wRC+ (100), 16th-best wOBA (.316), and eighth-highest strikeout rate (24.5%) across the last 14 days, via FanGraphs. An injury to C Ryan Jeffers is also expected to put a dent in Minnesota’s offense.

Tolle, who is Boston’s No. 1 prospect, has been a major bright spot for the Red Sox, residing in the 93rd percentile in xERA (2.43) and 91st percentile in xBA (.191).

In a loaded American Rookie of the Year race, “Yes” for Tolle to win the award carries an 11.11x payout, via PrizePicks Team Picks.

Over the same 14-day span mentioned above for the Twins, the Red Sox have tallied the 14th-worst wRC+ (97), 12th-best wOBA (.318), and 11th-best ISO (.155).

Twins vs. Red Sox Winner Payout, Over/Under – Friday, May 22

The Red Sox enter Friday’s game as home favorites, returning a 1.61x payout if they win outright, via PrizePicks Team Picks.

Here are the full payouts for the Twins vs. Red Sox game on PrizePicks.

• Spread: Red Sox -1.5 (2.32x payout)
• Over/Under: 7.5 (1.92x payout on Over)
• Game Winner Payout: Twins 2.22x | Red Sox 1.61x

Play the Twins vs. Red Sox winner or over/under on PrizePicks Team Picks to earn real money — available in 35 states!

Team Picks data is live at the time of writing and is subject to change.

Twins vs. Red Sox Prediction on Over/Under – 5/22/26

Here are the key game stats and trends behind our Twins vs. Red Sox prediction on the run total for Friday, May 22.

Lock in your Twins vs. Red Sox prediction on PrizePicks before the first pitch.

• While the Twins have the fifth-highest ISO (.157) on the road this season, they also have just the 15th-best wOBA (.312) and the eighth-highest strikeout rate (24.5%) in that split.
• On the other hand, the Red Sox have been unproductive at Fenway Park, logging the second-worst wRC+ (71), third-worst wOBA (.286), worst ISO (.106), and 12th-highest strikeout rate (21.7%) at home during the 2026 MLB season.
• With Boston’s woeful home metrics, they have the second-lowest rate of hitting the over at home (23.8%) this season.
• One concern about the total is that the Twins’ bullpen has the second-worst xFIP (4.94) and third-worst BABIP (.312).
• At the same time, the Red Sox’s relievers possess the sixth-best xFIP (3.78) and fifth-best BABIP (.261).
• Although Minnesota is going to load up on right-handed hitters, Tolle has been better against righties, posting a 3.64 xFIP, 0.71 WHIP, and 0.40 HR/9 in that split. Against lefties, he has a 4.28 xFIP, 1.00 WHIP, and 2.25 HR/9.
• Prielipp has also excelled against right-handed sluggers, tallying a 3.52 xFIP and 0.95 WHIP in that split. For context, he has a 4.88 xFIP and 1.00 WHIP when facing left-handed sluggers.

Twins vs. Red Sox Player Picks, Stats for PrizePicks – 5/22/26

Here are the top Twins vs. Red Sox picks to target on PrizePicks for Friday, May 22. Today’s MLB picks for PrizePicks include Payton Tolle and Connor Prielipp.

Red Sox SP Payton Tolle vs. Twins: 5.5 Strikeouts

• Tolle is in the 76th percentile in strikeout rate (26.1%) and 60th percentile in chase rate (31.7%) across his first five starts in 2026.
• Along with Tolle’s other stellar numbers against righties, he’s notched a 29.3% strikeout rate in that split.
• Plus, Tolle has been lights out at home this season, earning an elite 2.18 xFIP, 0.91 WHIP, and 35.7% strikeout rate.
• Although the Twins have the 11th-lowest strikeout rate against southpaws (21.4%), they have the sixth-highest swinging strike rate (11.6%) and the fourth-highest first-strike percentage (62.6%), so Tolle can get ahead in counts often.

Add Payton Tolle to your PrizePicks Lineup now.

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Twins SP Connor Prielipp vs. Red Sox: 4.5 Hits Allowed

• Even though the Red Sox are going to trot out a decent amount of righties, Prielipp has permitted a .261 wOBA, .253 OBP, and .190 BABIP in that split this season.
• Prielipp has given up fewer than 5 hits in each of his first five starts.
• At home, the Red Sox have the fifth-worst OBP (.300) and 14th-worst BABIP (.277).
• Up to this point, Prielipp has pitched into the sixth inning just once over his five outings, so there’s a chance he’s pulled before having the opportunity to surrender 5 or more hits.

Add Connor Prielipp to your PrizePicks Lineup now.

Make Twins vs. Red Sox Picks on PrizePicks

It’s been a disappointing start to the season for both the Twins and Red Sox, as each squad looks to get on track with young and talented left-handed starters on Friday. With Prielipp and Tolle dealing on the mound, runs could be tough to come by at Fenway Park.

Don’t wait until the first pitch happens — make your Twins vs. Red Sox picks on PrizePicks now and earn real money if you’re right.

Pick players, predict More or Less on their stats, and cash in if you’re right. With Team Picks, you can make predictions on game winners, spreads, and over/unders, now available in 35 states.

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