Senegal begin their quest for a first continental title on Monday with a Group B game against comparative minnows Zimbabwe at the Stade Kouekong in Bafoussam.
Africa’s top ranked team enter the tournament beset by expectation and weakened by temporary withdrawals due to the coronavirus.
Before leaving Senegal, the country’s president Macky Sall told the squad to bring back the trophy.
Six players including reserve goalkeeper Alfred Gomis all remained in Dakar after testing positive for the disease.
With the presidential directive still ringing in their ears, first choice goalkeeper Edouard Mendy - a Champions League winner with Chelsea - as well as skipper Kalidou Koulibaly succumbed to the disease in Cameroon along with striker Famara Diedhiou.
Third choice keeper Seny Dieng is set to start on Monday afternoon.
"It's a difficult and complicated situation," said Senegal coach Aliou Cissé ahead of the match against Zimbabwe.
"But we are going to be competitive and those who will go out onto the field are going to play for those who are absent.
"We are still going into the game against Zimbabwe full of confidence.”
And they should. Runners-up in 2019, they lie 100 places above the Zimbabweans who have never reached the knockout stages in their four previous appearances.
But Zimbabwe will be emboldened and keen to exploit the fragility.
Cameroon 2021 is their third consecutive appearance at the tournament - an unprecedented feat for Zimbabwe since it gained independence in 1980.
Guinea, under former international striker Kaba Diawara, take on Malawi in Group B at the same time as Group C begins with a clash between Ghana and Morocco at the Stade Ahmadou Ahidjo in Yaoundé.
The sides are both expected to progress to the last 16 but with Gabon lurking, it could be as one of the four best third-placed teams.
Were Comoros to occupy such a slot from Group C come the second phase later this month, it would be a huge achievement for the nation of less than a million souls competing in their first Cup of Nations.
“If you get to a tournament like this, then you’re likely to meet the big teams,” said head coach Amir Abdou in an interview just before the tournament.
“But the pressure will not be on us,” added the 49-year-old who also coaches FC Nouadhibou in Mauritania.
“It will be on the so-called big opponents. They have to ask how they will approach the game against us.”
Morocco boss Vahid Halihodzic would probably respond: “With discipline, mon ami.”
The veteran coach displayed his renowned iron-fist in the run-up to the tournament with the exclusion of the Chelsea forward Hakim Ziyech.
The two fell out early in 2021 and Ziyech was overlooked for the six 2022 World Cup qualifiers played between September and November.
Halilhodzic also left out the Ajax Amsterdam full back Noussair Mazraoui, who he accused in mid-year of feigning injury to avoid playing in a friendly, a charge Mazraoui has denied.
“Each team will have difficulties with players out due to the coronavirus,” said Halihodzic on Sunday.
“But we have to get on with it. It is no use crying or complaining. The team is hungry to do well and the Moroccan supporters are expecting us to have a good tournament. The squad is definitely ready to do something big.”