The Nigerian defender suffered a hamstring injury in training this week and now faces a battle to recover in time for the FA Cup semi-final against Manchester United at Wembley on 19 April.
Cahill was substituted at half-time in last weekend's win over Stoke after straining a calf but the injury has not proved as serious as first feared and the Australian has returned to full training, the club confirmed on Friday.
Everton manager David Moyes has spent most of the season grappling with injuries to key players and the loss of Yobo represents another headache.
Phil Jagielka can provide experienced cover but he has been filling in for another injured player, right-back Tony Hibbert, so Moyes could be forced to redeploy club captain Phil Neville from midfield to shore up his back four or use Danish international Lars Jacobsen instead.
Injury has deprived Everton of three first-team regulars: Victor Anichebe, Aiyegbeni Yakubu and Mikel Arteta, until the end of the season.
Despite their problems, Everton have not given up hope of a top four finish and a place in next season's UEFA Champions League with the win over Stoke leaving them just four points adrift of Arsenal and Aston Villa.
"Our target is still the teams above us," Moyes said. "There has been a momentum here for a few months with great attitude and spirit and the players have played wherever they have been asked to.
"We have always said we will try to hang onto the clubs above us and try to drag them back to us, but there is no doubt that Aston Villa and Arsenal are in the driving seat for the Champions League spots because they have the points on the board. We have to keep our form going to have any chance, and we will have to really go for it and hope they slip up."
Portsmouth, in contrast, are fighting for top-flight survival with only goal difference keeping them out of the drop zone. Caretaker boss Paul Hart will have to do without in-form winger Jermaine Pennant, who has torn a calf muscle.