The Red Sox grabbed a 1-0 lead against Pelfrey in the first inning and then scored four more in the second, the biggest blow coming on Will Middlebrooks' three-run double.
"Luckily the wind was blowing in. Otherwise, that might have been a grand slam," Pelfrey joked.
Pelfrey allowed six hits, five runs, three walks and notched two strikeouts, but manager Ron Gardenhire wasn't concerned about the right-hander's outing.
"I'm not a doctor, but the doctors tell me he's fine," Gardenhire said. "He's ahead of the curve. He's going to have his ups and downs, Every pitcher does, but he's fine."
Ryan Dempster, who signed with Boston as a free agent in December, fared much better. He yielded just one run, three hits, recorded three strikeouts and allowed two walks. He has now allowed three runs in four starts covering 12 2/3 innings this spring.
The right-hander pitched his way out of a jam in the second inning, as Parmelee worked a one-out walk and then took third on Joe Benson's double to left field. Dempster battled back and struck out Oswaldo Arcia and Eric Fryer to end the threat.
"When you go away from the season and the season ends, you lose sight of those situations a little bit, so when you get back into 'em, it kind of gives you an understanding of trying to manage an inning and how to maybe get a strikeout when you can," Dempster said.
Parmelee, who robbed the Orioles' Ryan Flaherty of a home run on Thursday night when he returned to the lineup in right field after missing nine games with a tight right groin, replaced Justin Morneau at first base on Thursday and homered in the fourth.
Up next: Right-hander Liam Hendriks, who is trying to secure the fifth spot in the starting rotation, is scheduled to start against the Red Sox at JetBlue Park on Friday night at 6:05 CT. The game will air live on MLB.TV. It will be Hendriks' fifth appearance of the spring, and the fifth of eight games between Minnesota and Boston.