Chris Morrow of Crusaders will be out of action for several months after sustaining a broken ankle in Monday's 2-2 draw with Linfield.
The long-serving midfielder is in plaster and his testimonial game against Derry City on 13 October has been postponed.
Morrow will be a spectator as the Crues, a point clear at the top of the table, take on champions Cliftonville.
Saturday's Seaview clash is the first north Belfast derby of the season.
It is a chance for Tommy Breslin's Reds, who have won just three out of 10 in the league so far, to move to within a point of their city rivals.
The league table is tightly-packed with just a five-point gap between the Crues and seventh-placed Glentoran.
"A couple of games ago we were sixth and we could drop back down there just as quickly. That is how close things are," said Crusaders Stephen Baxter.
"It is very early and we are just trying to stay up there in the top four where we have been for the last few seasons.
"Cliftonville will be looking for a big performance on Saturday as they are four points off the pace.
"I remember they started slowly last season but went on to retain their title."
Portadown, Ballymena and Linfield are all on 18 points, one behind the leaders, after 10 matches.
The Ports, disappointed to be held to a 2-2 draw by bottom club Warrenpoint last weekend, face a tricky trip to Institute.
"Our performances have been good this season but Portadown will be a big test for us," said Institute manager Paul Kee.
"They are up there in second and are looking to go top. They are side with experience and quality."
The teams in third and fourth go head-to-head at Windsor Park as Ballymena take on Linfield.
In their last home match, Linfield lost 1-0 to Glenavon and Warren Feeney's men face a Sky Blues team revelling in an encouraging start to the league campaign.
Glentoran, boosted by midfielder Marcus Kane's decision to sign a three-year contract extension this week, are unbeaten in their last five in the league but have yet to win on the road.
Dungannon, who have taken just two points from their last seven Premiership matches, entertain Coleraine at Stangmore Park.
Danske Bank Irish Premiership - Saturday, 4 October (15:00 BST)
Crusaders v Cliftonville
Dungannon Swifts v Coleraine
Glenavon v Glentoran
Institute v Portadown
Linfield v Ballymena United