Twins right-hander Phil Hughes took the loss, going 5 1/3 innings, giving up four runs on 10 hits and a walk with two strikeouts.
"I'm ready to go," said Hughes. "The pitch count is up. Obviously [I] went through a couple struggles here the last couple of outings, but that is going to happen and that is good to go through some adversity. Stuff-wise, I feel good, and I'm extended to where I can throw 100 pitches, so I'm ready."
The Red Sox scored two runs in the fourth when Mike Napoli walked with one out and scored on Mike Carp's two-out double. Xander Bogaerts' single scored Carp.
Napoli, who went 1-for-2 with two runs scored and an RBI, opened the sixth with his fourth Grapefruit League home run. Consecutive one-out singles by Carp, Ryan Dent and Derrik Gibson gave the Red Sox a 4-0 lead.
In his first two Grapefruit League outings, Doubront went a combined six scoreless innings, giving up just three hits. In his next two, though, he went eight innings, giving up 15 runs on 20 hits. Against the Twins Friday afternoon, he managed to pitch himself out of trouble. In the fifth, after giving up leadoff hits to Aaron Hicks and Eduardo Escobar, Doubront struck out Pedro Florimon, Jason Bartlett and Joe Mauer to end the threat.
Hughes, who is beginning his first season with the Twins after joining the team as a free agent in December, was making his fifth start. Over 19 innings, he's surrendered 12 runs (10 earned) on 26 hits and four walks with 12 strikeouts.
"Velocity-wise, fastball's coming out of his hands real good," said Twins manager Ron Gardenhire. "He got ahead in some counts and tried to throw some breaking balls that they got on in a couple of innings out there that he just didn't get them where he wanted to. But velocity's good. His arm strength's good. ... We like the way he's throwing."
Up next: Right-hander Mike Pelfrey is scheduled to make his sixth start when the Twins travel to face the Red Sox at JetBlue Park at 1:05 p.m. ET for their final Grapefruit League game on Saturday. Pelfrey is 1-0 with a 1.98 ERA in five outings spanning 13 2/3 innings. He has given up three earned runs on 11 hits with three walks and nine strikeouts.