While his average at Petco Park (.258) is well below his career average (.326), Pujols has hit seven home runs in 97 at-bats in San Diego.
The Padres will be matched up exclusively with the American League West in Interleague Play, including six games against their natural rivals -- and Spring Training partners in Peoria, Ariz. -- the Mariners.
That includes the Texas Rangers, who have appeared in the last two World Series and currently boast what is regarded as the most potent lineup in baseball, led by outfielder Josh Hamilton, who has never hit a home run at Petco Park.
When the Padres head to Seattle and Oakland for road games, they will have any number of options to use in the designated hitter spot. Facing a right-handed pitcher? Maybe Mark Kotsay gets a start. Or, if the Padres are going up against a left-handed pitcher, maybe Jesus Guzman will be the DH.
San Diego manager Bud Black has in the past used the DH spot to keep a big bat in the lineup, but maybe allow that player to take a game off from playing in the field. Third baseman Chase Headley and first baseman Yonder Alonso have played a lot early this season and could possibly see time as a DH.
Players to watch
Chase Headley, 3B (.414 in 2011): Headley feasted on American League pitching a year ago, as he hit a cool .414 with a .452 on-base percentage. He had four doubles, 20 singles and stuck out on 13 occasions. Headley has always done most of his offensive damage away from Petco Park.
Tim Stauffer, SP (1-2, 2.25 ERA): Stauffer's record in Interleague Play didn't reflect it, but Stauffer did his part against American League foes, posting a very good ERA. Stauffer missed the first six weeks of the season with a right elbow strain but rejoined the rotation on May 14.
Luke Gregerson, RP (2.45 career ERA): If the Padres get in a late-inning pinch, they know they can turn to Gregerson and his nasty slider. Gregerson doesn't have a ton of experience in Interleague Play (seven games), but does have 10 strikeouts in 7 1/3 innings.
Last year: The Padres were 6-9 in Interleague Play, though it sure could have been a lot worse. The team opened with seven consecutive losses against American League teams before winning six of eight to finish the schedule. That schedule included games against the Mariners, Twins, Red Sox and Royals.
All-time: Interleague Play has not been kind to the Padres, who are 103-136 in 15 seasons of play against American League teams. The team is 53-65 at home in Interleague Play and 50-71 on the road. The Padres were 9-6 in 2010. Two seasons before that, they were 3-15.
vs. Angels, May 18-20 Buy tickets: The Padres are 11-11 against the Angels, though they haven't played them since 2009. During that series in Anaheim, the Padres were swept in three games and were also outscored 26-7. The Padres will have more than just Pujols to contend with, especially with the way Mark Trumbo and Mike Trout have been swinging the bat lately.
at Mariners, June 12-14 Buy tickets: The first of two series against the Mariners this season. The Padres actually have the same Interleague Play record at home against Seattle (18-22) as they do in games away from San Diego. For what it's worth, Ichiro Suzuki is a career .341 against the Padres. These two teams will meet again on June 22-24 at Petco Park.
at A's, June 15-17 Buy tickets: The Padres face the A's for the first time since 2009, when Oakland took two of three games from San Diego at Petco Park. The Padres could run into A's pitcher Tyson Ross, the older brother of 2011 first-round Draft pick, pitcher Joe Ross. Also, infielder Eric Sogard was drafted by the Padres, but later traded to the A's.
vs. Rangers, June 18-20 Buy tickets: The Padres will attempt to cool the Rangers' red-hot bats at Petco Park as these two teams meet for the first time since 2009 when the Padres won the final two games of a three-game series in Arlington. How will the Rangers' big thumpers fare at spacious Petco Park?
Corey Brock is a reporter for MLB.com. Keep track of @FollowThePadres on Twitter. This story was not subject to the approval of Major League Baseball or its clubs.