Amakhosi are wounded having lost 1-0 to Polokwane City at home in a PSL match two weeks ago.
The defeat ended the Soweto giants' four-match unbeaten run and they will be keen to return to winning ways in Cup competition.
Chiefs, who were eliminated from the 2018 MTN8 by SuperSport United in the semi-finals, are desperate to end their three-year trophy drought.
The Glamour Boys are the most decorated club in the history of the League Cup (Telkom Knockout) having won it a record 13 times.
|Game||Kaizer Chiefs v Black Leopards|
|Date||Sunday, October 21|
|Time||15:30 pm SA Time|
TV Channel, Live Score & How To Watch
In South Africa, the game will be shown live on SuperSport 4. You can also catch live updates on Goal.com .
|Live Match Centre||TV Channel|
Squads & Team News
Amakhosi head coach Giovanni Solinas will be hoping that Khama Billiat shrugs off his injury and features against Leopards.
The Zimbabwe international has hit the ground running at Chiefs and he has the ability to inspire the team to victory.
Daniel Cardoso, Lebogang Manyama, Joseph Malangoane and Andriamirado 'Dax' Andrianarimanana are all out nursing injuries.
Meanwhile, Leopards are heading into the Cup clash having lost 1-0 to Lamontville Golden Arrows away in a PSL match two weeks ago.
This was Lidoda Duvha's fourth defeat in their last five matches having secured a win over Baroka, before facing Arrows.
The last time they participated in the Telkom Knockout was in 2012 and they lost 2-0 to Orlando Pirates in a round of 16 match.
The Limpopo side has never won this tournament and Joel Masutha's side will be hoping to overcome Chiefs, and go all the way in this year tournament.
Leopards head coach Joel Masutha will look to Zambian marksman Mwape Musonda, who remains his main striker.
The former Pirates striker will be keen to find the back of the net against Amakhosi and help his side advance to the next round.
Chiefs and Leopards have met in five previous cup matches, four of which have been won by the former.
The last time the two teams clash was in 2015. Leopards claimed a surprise 2-1 win in the Nedbank Cup clash thanks to goals from Morgan Shivambu and Roggert Nyundu.
In total, Chiefs and Leopards have clashed in 23 matches across all competitions since 2001/02.
Amakhosi have recorded 13 wins compared to six for Lidoda Duvha, while just four matches have been drawn.