Reds will be without fly-halves Ben Lucas and Mike Harris for around a month after they hobbled off in the defeat at the Sharks.
The pair suffered hamstring injuries in the 27-22 loss and have been forced to make an an earlier than expected return to Australia.
They will fly back from the tour of South Africa on Monday to commence a rehabilitation process which will keep them out of action for a minimum of three weeks.
The overall injury situation at the Reds, magnified by the loss of Lucas and Harris, has forced coach Ewen McKenzie to look outside his normal squad for replacements and he has selected backs Joel Rapana and Nathan Eyres-Brown to join the team in South Africa.
Rapana, 25, represented Queensland A in their final two games of the 2012 Pacific Rugby Cup tournament earlier in the year and has previously featured at Super Rugby level for the Western Force, his debut coming against the Hurricanes in 2010.
"Losing your two healthy goal kickers and playmakers at the number 10 position is far from an ideal scenario, but we'll reassess in coming days and come up with a plan best suited for our final game on tour against the Bulls," coach Ewen McKenzie said.
"We are extremely disappointed to have lost to the Sharks but it was arguably our best attacking performance of the season and there are a number of positives we'll take from the match. We are heading in the right direction with how we want to play the game."
The Reds enter their round five contest against the Bulls as leaders of the Australia Conference with their 27-22 loss to the Sharks their first defeat of the season following earlier successes over the Waratahs, Force and Rebels.
The Reds were triumphant in their last encounter against the Bulls, a 39-30 victory at Suncorp Stadium, although haven't overcome the South African heavyweights in Pretoria since 2001.