"It's been a frustrating year, frustrating night, just keeps adding on and I'm getting tired of it," Lester said. "I try to make adjustments, try to do the things I need to do and I'm just not getting results."
Lester had a chance to get out of the fourth inning unharmed, but Youkilis crushed a 3-2 pitch for his fourth homer since being traded to Chicago on June 24.
"Bad location, bad spot, bad time, all of the above," Lester said.
In two games against his former employer, the third baseman is 4-for-8 with two doubles, a home run, three runs scored and three RBIs. As he rounded the bases after putting the home team behind, 6-2, Youkilis still heard cheers from the crowd.
"You never know here. It's been great," Youkilis said. "The fans have been unbelievable, and I can't thank them enough and all the kind things they keep saying from the fans every day. It's been great and not too many opponents get to come in here and have that opportunity. Usually, it's a little more negative toward the opposition. I've enjoyed it and have fun and have two more games here."
Boston's rotation had been a strength for the club in the first four games of the second half, but Lester's start fell well below the standards set before him.
The four-inning outing tied for Lester's second shortest of the season. He lacked command and walked three against four strikeouts, throwing 91 pitches and allowing seven hits. He fell to 5-7 and his ERA jumped to 4.80.
"We just had trouble getting ahead of guys in the count," said catcher Jarrod Saltalamacchia. "I thought he made some good pitches, had some good stuff, but we had to just get ahead and stay ahead."
Lester is mired in the worst stretch of his career. He's allowed six runs or more three times in starts lasting four innings or fewer, the first time he's done so in his career. Lester has given up at least one run in the first inning in each of his last four starts, his longest stretch ever.
Over his last two starts, Lester has given up 10 earned runs on 16 hits in 8 1/3 innings. In three career outings against the White Sox at Fenway Park, he's 0-2 with an 8.82 ERA.
"It's frustrating showing up every day busting my [rear] and going out there busting my [rear] when I pitch and just not pitching well," Lester said. "I'm letting my team down. I haven't been doing it all year."
The Red Sox looked like they might give their struggling ace some much-needed run support after Carl Crawford and Adrian Gonzalez each had RBI singles in the first inning. Instead, Chicago starter Phil Humber settled in and blanked Boston over his final five frames.
Starting in left field in only his second game of the season following wrist and elbow injuries, Crawford had another productive game for the Red Sox. He had three hits, three steals and scored two runs.
"Carl is playing with a real fire and that's a good thing to see," said Red Sox manager Bobby Valentine.
Gonzalez and Jacoby Ellsbury also had two hits apiece off Humber, but the rest of the Red Sox lineup combined to go 0-for-15 against the right-hander.
Kelly Shoppach hit a pinch-hit, two-run homer in the eighth inning to cut the deficit to 7-5, but it was not enough to overcome Lester's rough start.
Will Middlebrooks, who took over for Youkilis as the everyday third baseman, went 1-for-4 with an RBI single.
Junichi Tazawa threw four innings of one-run ball in relief of Lester to preserve the bullpen. The right-hander struck out four in the longest relief appearance of his career.
"Tazawa was fantastic," Valentine said. "He gave us four big innings and saved the bullpen and kept us in the ballgame."