Howard, who was leading the NL with 81 RBIs, went on the disabled list Tuesday because of a sprained left ankle. The Phillies said the sprain was moderate.
"We're hopeful he'll be back in two weeks," general manager Ruben Amaro Jr. said. "It may be longer than that. We're not sure."
The 2006 NL MVP was hurt Sunday while sliding into second base at Washington. He traveled with the team to Miami, but when swelling in the ankle became worse, he returned to Philadelphia for an MRI exam Tuesday.
Howard is the 15th Phillies player to go on the disabled list this season. Shane Victorino and Chase Utley are also sidelined now, leaving the two-time defending NL champions without a big chunk of their offense as they try catch first-place Atlanta in the East.
When asked what kind of challenge the Phillies face in Howard's absence, manager Charlie Manuel said: "It's a big one. ... We've only had our starting lineup six or seven games since the season started. We've got to get well, and we've got to keep going."
The move involving Howard was retroactive to Monday. John Mayberry Jr. was recalled from Triple-A Lehigh Valley and will join the team Wednesday.
Howard was in an 0-for-14 slump when hurt but was still hitting .292 with 23 homers. Tuesday's game was only the second he hasn't started this season.
Howard was examined in Philadelphia by team physician Michael Ciccotti, who determined the injury involves two ligaments on the outside of the ankle.
"The good news is that it wasn't a severe ankle sprain," Amaro said, "in that it only affected the lateral side" -- the outside.
Howard was injured scrambling back to second base after a throw from right field. He was helped off the field by Manuel and a team trainer.
"It's a little bit more serious than I thought it was," Manuel said. "The other day I didn't think it was going to be quite a while [that Howard would be out] because he told me, 'Chuck, I'll be all right.'
"But once I saw it on TV -- his ankle came under him, and all his weight was on his ankle. When he got back to the hotel, it started swelling up, and the next day, according to the trainers, it was puffed up pretty good."
One bit of good news for the Phillies: Left fielder Raul Ibanez, who missed Sunday's game because of a sore left wrist, was back in the lineup Tuesday.