Amakhosi are currently chasing a top three finish to their season, currently in third place with 48 points from 27 games, five clear of AmaZulu in fourth place.
They have enjoyed an impressive second half of the season, while Sekhukhune have struggled for results.
Babina Noko recently dispensed with head coach Eric Tinkler after a poor run of form that saw the club drop from third to fifth, with 42 points.
Paulus Masehe has since taken charge of Sekhukhune and is hoping to build on a 3-1 win over a struggling Chippa United last time out, and previous 1-1 draw with Marumo Gallants.
Chiefs though will be buoyed by their 1-1 draw with title-chasing Mamelodi Sundowns in their last encounter, and will be eager to end their campaign with maximum points.
While Sekhukhune play Chiefs, Richards Bay and Siwele in their final three games of the campaign, Amakhosi complete their season against AmaZulu and Chippa.
In team news, Chiefs midfielder Siphesihle Ndlovu will miss the tie through suspension.
Speaking ahead of the game Chiefs co-coach Khalil Ben Youssef said on SuperSport: "We are always thinking about ourselves, about our performances.
"Every training session and at our meetings, I said the same thing because if this team performs very well, no-one can stop us in the league.
"The process is there. There is a big difference this season from last term. The results are there. We have three games [remaining] and we have to fight for maximum points."
Masehe said in the Herald: "The main goal is to get three points against Kaizer Chiefs.
“The approach and attitude, the intent, are going to be the same as we have been playing.
"Obviously this season Chiefs have improved, hence they are sitting where they are now on the log, which we have to respect — but we have our own road to travel and objectives.
"Unfortunately they are in our path and we have to face them."
Sekhukhune won the first round tie at the FNB Stadium 3-1 with goals from Bradley Grobler (2) and Thabang Monare, with Flavio Silva on target for Chiefs.
