Then, the Red Sox open Fenway Park for business with three games against a loaded Tigers squad and three more against the always star-studded Yankees.
There will be no rest for the weary after that daunting six-game homestand. The Sox immediately go to Cleveland and do battle for two games with the team that took them to seven games in the American League Championship Series in 2007. And then? Two more games against the Yankees, this time in New York.
Once the Sox depart the Bronx, they get a brief dropoff with four games against the Rangers, who finished in last place in the AL West a year ago.
But after that, it picks right up when the defending AL West champion Angels come to Fenway for the first time since last October's Division Series. Then it's off to Tampa Bay for three games against the young and improving Rays. And April concludes with three home games against the Blue Jays.
Under any circumstance, that would be an unusually rough slate of games. Consider, however, that the Red Sox are doing this after jet-setting to Tokyo, and then to Los Angeles and Oakland.
"If we play teams like Detroit and the Yankees and Cleveland and they beat us, it's going to be called jet lag," said Red Sox manager Terry Francona, who immediately dismisses any kind of excuse no matter how these battles with the titans wind up.
"They're pretty good teams," Francona said. "We just need to play good baseball."
Since Francona took over the Red Sox in 2004, the team has typically gotten off to a fast start. That might be tougher than ever this season.
"We knew the first month would be tough with our long road trip and coming back and playing the teams we have to play," said Sox second baseman Dustin Pedroia. "We're not going to make excuses. We understand it's going to be a tough road, but we have to find a way to win."
That's the type of culture the Red Sox have built while winning the World Series twice in the last four years.
The iron of the American League? That's exactly what the Red Sox will see for the rest of April. Talk about an early test for the defending World Series champions.
"You've got to play them eventually," said catcher and captain Jason Varitek. "We don't back down to any challenge here."
Perhaps it can be viewed as a measuring stick.
"I don't mind it," said Red Sox third baseman Mike Lowell. "I think any time you play a team that's supposed to make the playoffs, you want to play well and see how your guys measure up. Really, whether we win or lose these series will not determine whether or not we make the playoffs. Not right now at least. But still, they're important games, they're big games. I think we're looking forward to it because they want to see how they measure up with us as well."
Red Sox general manager Theo Epstein isn't big on April baseball from an evaluation standpoint.
"The early part of the season is not always a real good indicator," said Epstein. "We've been fortunate to get off to good starts but everything is exaggerated early on. As far as I'm concerned, I'd like to go off and scout for the draft and do something else until about the end of April because then you get into a good rhythm and see how things are really going. Unfortunately you don't always have that luxury in Boston.
"But I'm not a big fan of the early-season. It would be nice to get off to a good start. We have a tough schedule this April, more so because of who we're playing than the travel involved. We'll do our best."
They'll definitely be playing against the best.
"That's fun for the fans because we're obviously one of the better teams too, so it's going to definitely be some enjoyable baseball to watch and be a part of," said Sox center fielder Coco Crisp. "We'll see what happens."