"It's one of those games. We just couldn't find a way to get to him," said second baseman Dustin Pedroia. "He located every pitch. He kept us off-balance. He was pretty darn good tonight."
A victory would have put the Red Sox above .500 for the first time this season, but instead, they suffered a tough-luck defeat.
Lefty Felix Doubront certainly deserved a better fate than a loss after allowing four hits and two runs over six innings, walking two and striking out a career-high nine batters.
"Well, Felix Doubront had his good stuff," said manager Bobby Valentine. "You know, a walk and a home run. Boy, he was battling the whole way. He just happened to pick tonight, when the opposing pitcher had good stuff and shut us down."
The Orioles produced only one rally off Doubront, and it came in the second inning. Wilson Betemit drew a leadoff walk and that came back to haunt Doubront when Steve Tolleson hammered a two-run homer to left-center.
That was hardly a sign of things to come for the Orioles against Doubront, as the lefty simply shut them down the rest of the night.
"Those things happen. It's a tough game," said Doubront. "I just tried to stay calm and go deep in the game to give us a chance to let our guys do their job and score some runs."
Meanwhile, the Red Sox got a big swing in the top of the fourth when Youkilis celebrated his return from the disabled list by ripping a solo homer to center, slicing Baltimore's lead to 2-1.
Youkilis looked like a far more dangerous hitter than he did before going on the disabled list.
"Boy, that's as good a swing as I've seen Youk have," said Valentine. "He hit it to center field with power. He was sprinting around the bases. That was a good sight."
If Youkilis can keep that up, it could be a big lift for Boston.
"He's a great player," Pedroia said of Youkilis. "We've seen over the years what he does and what he does for our team. It's exciting to have him back."
Boston's only other hit was an opposite-field single by Adrian Gonzalez in the second.
"They both threw the ball great," Gonzalez said. "Both pitchers did a good job, just came out on the wrong end of it."
Other than the homer by Youkilis, Boston was stifled by Matusz and Baltimore's bullpen.
"It's a good team that's on top of their game offensively, and to have that type of outing in a much-needed situation is impressive," said Orioles manager Buck Showalter.
The Red Sox hoped they would need just one swing to tie it in the ninth, but that changed when Matt Albers surrendered a two-run bomb to Betemit with two outs in the eighth.
Even with the heart of the order up, Boston went 1-2-3 in the ninth.
The teams will play the rubber match of this three-game series on Wednesday afternoon at Camden Yards.
If the Red Sox can win that one, they'll finish the road trip with a 5-3 mark.
"It's always important to win against your division, especially guys like Baltimore, who are in the lead," said catcher Jarrod Saltalamacchia. "You want to try to close the gap up a little bit. We're looking to go out there tomorrow and continue what we've been doing. Tip your cap tonight. He pitched a great game. We'll go tomorrow and try to put runs on the board."