Guy-Brice Parfait Kolélas died on a flight to France for treatment, the director of his campaign said.
Hours ago the 61-year-old actress appeared in a video interviewed on social media, in which she removed an oxygen mask and told her fans she was "fighting death".
He urged them to vote in Sunday's election.
The election law does not cancel an election if one of the candidates dies.
Mr Kolélas, a diabetic, was one of six opponents of President Denis Sassou Nguesso, 77, who has been in power since 1979, five years after the 1992 election defeat.
Congo-Brazzavile has officially recorded more than 9,000 cases of Covid-19 and 130 deaths.
The country has imposed a night clock rule in the two largest cities of Brazzaville and Pointe-Noire and closed its borders due to the epidemic.
However, campaign rallies are allowed, with not many signs of people respecting social distance or wearing a mask.
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Mr Kolélas missed his last campaign event on Friday a day before saying he feared he had malaria, the Associated Press agency reported.
He was admitted to a private hospital in the capital, Brazzaville, and was later diagnosed with Covid-19.
Speaking in French on his hospital bed, Mr Kolélas said: "My dear people, I am in trouble. I am fighting death. But please stand up and vote for change. I would not fight in vain."
"Stand up as one ... I am fighting on my deathbed, and you are fighting for your change," he urged his supporters, saying the election was "the future of your children."
The head of the government's Covid-19 response team, Elira Dokekias, said Mr Kolélas' condition was critical on Saturday, the Associated Press reported.
After casting his vote in the capital, Mr Sassou Nguesso wished the former fishing minister and son of former Prime Minister Benard Kolélas a speedy recovery.
A large crowd gathered on Sunday to see captions of the president, many people without masks and failing to follow social rules.
Mr Sasou Nguessou defeated Mr Kolélas in the last 2016 election, receiving 60% of the vote compared to his 15%.
The NetBlocks monitoring group reported that the internet was blocked before voting on Sunday.
The largest opposition party, the Pan-African Union for Social Democracy (UPADS), is boycotting the election, saying it fears the polls could divide the nation.