Cameroon, who are hosting the tournament, booked their place in the quarter-finals with a 2-1 victory over minnows Comoros on Monday night.
However, prior to kick-off at The Paul Biya Stadium, at least eight people died and 50 were injured on their way to the stadium.
It is understood supporters were involved in a crush as some ticket-less fans attempted to access The Paul Biya Stadium, a 60,000 capacity arena named after Cameroon's president.
Videos online show scenes of panic outside the ground and reports claim several children were caught up in the incident.
A statement from the Confederation of African Football read: "CAF is aware of the incident that took place at Olembe Stadium during the TotalEnergies Africa Cup of Nations fixture between hosts Cameroon and Comoros tonight, 24 January 2022.
"CAF is currently investigating the situation and trying to get more details on what transpired.
"We are in constant communication with the Cameroon government and the Local Organizing Committee.
"Tonight, the CAF President Dr Patrice Motsepe sent the General Secretary, Veron Mosengo-Omba to visit the supporters in hospital in Yaounde."
The stadium was built in preparation for the delayed competition, which kicked off earlier this month.
Stadiums have been operating at 80 per cent capacity during the Africa Cup of Nations due to restrictions placed on organisers because of the coronavirus pandemic.
Premier League club Everton tweeted: "The thoughts and prayers of everyone at Everton are with the families of those fans who have lost their lives and anyone affected by the tragic events at today's #AFCON2021 match between Cameroon and Comoros in Yaounde. RIP."
Cameroon won the game 2-1 to set up a quarter-final date with Gambia.
Jimmy Abdou was sent off after seven minutes as Comoros, minus a recognised goalkeeper due to injury and coronavirus, saw their fairytale run end.
Comoros, ranked 132 in the world, were without the injured Salim Ben Boina for the round-of-16 tie in Yaounde while fellow goalkeepers Ali Ahamada and Moyadh Ousseini had both tested positive for Covid-19.
Ajaccio's 5ft 8in left-back Chaker Alhadhur took over in goal for a Comoros side who were without several outfield players and coach Amir Abdou to coronavirus.
Karl Toko Ekambi and Vincent Aboubakar were on target as Cameroon secured a quarter-final date with Gambia, but it was not without concern as Youssouf M'Changama thundered home a 30-yard free-kick nine minutes from time.