The clash between South Africa and Botswana will be a repeat of the 2016 Cup final and the 2018 Plate decider as the familiar foes clash again for a place in the semifinals, with Bafana Bafana coming out on top in both those matches.
East African guest nation Uganda will have to get past Lesotho to advance to the Last 4, but will be wary of a Likuena side that has finished in third place in the last two installments of the COSAFA Cup.
Defending champions Zimbabwe will meet the winner of the first round Group A, which will be one of Angola, eSwatini, Comoros and Mauritius.
Angola, like Zimbabwe, will be heading to the 2019 Africa Cup of Nations in Egypt shortly after the tournament and that would be a massive quarterfinal line-up were it to materialise.
Comoros, meanwhile, are appearing in their first COSAFA Cup since 2009, a welcome return for the islanders after a decade on the sidelines.
Zambia, always a power in the regional showpiece competition, will clash with the winner of Group B, which includes Mozambique, 2015 winners Namibia, Malawi and Seychelles.
Namibia are another side that are plotting their trip to the Cup of Nations finals, but Mozambique and Malawi in particular will present a mighty challenge.
The four winning quarterfinals advance to the Cup semifinals, while the losing teams will move in to the Plate competition.
2019 COSAFA Cup draw:
Zambia vs Winner Group B
Lesotho vs Uganda
Zimbabwe vs Winner Group A
South Africa vs Botswana