With Carles Puyol, Eric Abidal and Adriano also on the medical list, Guardiola has a severe defensive headache as Barca prepare for Wednesday's Champions League semi-final first leg away to a Real Madrid side now bristling with confidence.
The silver lining to the dark cloud of injury news was Villa's goal in a laboured 2-0 La Liga win at home to Osasuna on Saturday, the Spanish striker's first in 12 games in all competitions.
"The most important thing is that the team scores and wins," said Villa, who was visibly relieved after his goal in the 24th minute at the Nou Camp, his 18th in the league this season.
"There is time now to rest and to think about the first leg of the Champions League semis," the striker told reporters, as Barca maintained their eight-point lead over Real with five league games left to play.
It was unclear how long Milito (calf) and Maxwell (groin) would be out of action, Barca said on their website following scans on Sunday.
Puyol trained apart from the rest of the squad on Sunday, while Abidal and Adriano are unlikely to play again this season.
Last week's dramatic King's Cup Final victory over Barca has provided a palpable boost to Real coach Jose Mourinho and his players and they romped to a 6-3 win at third-placed Valencia on Saturday despite resting several key squad members.
Striker Gonzalo Higuain netted three on Real's return to the Mestalla stadium, three days after victory there earned them a first domestic cup since 1993, and playmaker Kaka scored twice as the pair continued their comeback from injury.
POWER SHIFT
Real's cup win came after a 1-1 draw at home to Barca in La Liga, a result which helped banish memories of their 5-0 drubbing at the hands of the Catalan club in November's league game at the Nou Camp.
Guardiola admitted that the balance of power had shifted to the Spanish capital since then.
"We know that Madrid are not going to lose any more (league) games because with a title in the bag they are liberated and we have to get back to winning ways," he told a news conference after the Osasuna game.
"We are not going (to Madrid) in the best condition but in mental terms we will travel to the Bernabeu with a lot of enthusiasm," he added.
"We accept that Madrid are favourites, they have earned that in the last few weeks, and we'll try to turn that around."
Barca midfielder Sergio Busquets, whom Guardiola has deployed as a makeshift centre-back in recent weeks together with Javier Mascherano, said injuries could not be used as an excuse for failure at this crucial stage of the season.
"The more players we have available the stronger we are, as that means the coach has more options," Busquets said at a news conference on Sunday.
"But there are no excuses now and we can't allow fatigue to be an issue either."
The return leg of the Champions League semi-final is at the Nou Camp on May 3. The winners of
