Last year, the Bulls shocked the Hurricanes in the first round, then lost four consecutive matches and finished 12th.
They began this season with a 40-3 triumph over the Stormers only to suffer a heavy 27-12 defeat by the Jaguares in rain-lashed Buenos Aires last weekend.
Playing away to the Lions, runners-up in the past three Super Rugby finals, is a tough task at the best of times, and they must front up on Saturday without Springbok lock De Jager.
He hurt his shoulder in Argentina and will also miss the fourth-round clash with the Coastal Sharks in Pretoria.
Stand-in skipper and flyhalf Handre Pollard is conscious of the need to avoid another early-season collapse.
"Losing Lood for at least two matches is a massive blow and the rest of us must ensure we get back on the winning trail this weekend," Pollard said.
Saturday's clash at Ellis Park is scheduled for 15:05.
Teams:
Lions
15 Andries Coetzee, 14 Ruan Combrinck, 13 Lionel Mapoe, 12 Harold Vorster, 11 Aphiwe Dyantyi, 10 Elton Jantjies 9 Nic Groom, 8 Hacjivah Dayimani, 7 Marnus Schoeman, 6 Kwagga Smith, 5 Stephan Lewies, 4 Rhyno Herbst, 3 Carlu Sadie, 2 Malcolm Marx (captain), 1 Dylan Smith
Substitutes: 16 Pieter Jansen, 17 Sti Sithole, 18 Frans van Wyk, 19 Robert Kruger, 20 Vincent Tshituka, 21 Ross Cronje, 22 Franco Naude, 23 Courtnall Skosan
Bulls
15 Warrick Gelant, 14 Cornal Hendricks, 13 Jesse Kriel, 12 Dylan Sage, 11 Rosko Specman, 10 Handré Pollard (captain), 9 Embrose Papier, 8 Duane Vermeulen, 7 Hanro Liebenberg, 6 Ruan Steenkamp, 5 Eli Snyman, 4 Jason Jenkins, 3 Trevor Nyakane, 2 Schalk Brits, 1 Lizo Gqoboka
Substitutes: 16 Corniel Els, 17 Simphiwe Matanzima, 18 Dayan van der Westhuizen, 19 Jannes Kirsten, 20 Tim Agaba, 21 Ivan van Zyl, 22 Manie Libbok, 23 Divan Rossouw