Orlando Pirates lose three matches, coach within eight days
The Soweto side, whose popularity in the republic is matched only by arch rivals Kaizer Chiefs, slumped 1-0 at home to Highlands Park in a South African Top 8 Cup quarter-final.
Last Saturday, former African champions Pirates fell 1-0 away to Green Eagles of Zambia in the first leg of a CAF Champions League preliminary tie.
On Wednesday, they were humbled 3-0 by SuperSport United in the second round of the Premiership with captain Happy Jele publicly slamming team-mates during a half-time huddle on the pitch.
Sredojevic resigned late Friday as his third season with Pirates was getting under way, saying he wanted to be with his gravely ill mother in Serbia.
He rejected as "nonsense" reports that he was leaving Pirates to join Zamalek of Egypt or Wydad Casablanca of Morocco, who are among the most successful and best supported African clubs.
"My mother is battling breast cancer," he told the South African media. "She has been undergoing chemotherapy and I need to be at her side."
Rhulani Mokwena, the senior assistant to Sredojevic, was promoted to caretaker coach just hours before the quarter-final.
"A lot has been happening at the club, but that is no excuse for the latest loss. We accept this defeat with utmost humility.
- 'Problem' -
"Playing twice every week is a problem as we rely heavily on video sessions to solve problems when we should be spending more tie on the training field."
Pirates face AmaZulu away Tuesday in the Premiership, then Green Eagles at home in the Champions League four days later.
Substitute Wayde Jooste scored for Highlands Park with eight minutes remaining at Orlando Stadium in Soweto and Pirates supporters sat stunned in the stands after the final whistle.
In Cape Town, trophy-holders Cape Town City fell at the first hurdle in defence of the title when shocked 2-0 by Polokwane City.
A goal in each half, from Ghanaian Mohammed Anas and Zimbabwean Charlton Mashumba, delivered victory for a Polokwane side coached by Serb Zlatko Krmpotic.
Meanwhile, reigning Premiership champions Mamelodi Sundowns avoided joining Pirates and Cape Town on the scrap heap by coming from behind to win 3-1 at home against Bloemfontein Celtic.
After a scoreless first half, Ndumiso Mabena put Celtic ahead only for the 2016 African champions to respond with three goals in 15 minutes from Themba Zwane, Musa Lebusa and Keletso Makgalwa.
The remaining quarter-final, between Bidvest Wits and SuperSport United, is scheduled for Johannesburg Sunday.
The Top 8 Cup features clubs who finished first to eighth in the previous league season and offers a winners-take-all eight million rand ($520,000/470,000 euros) prize.