De Laurentiis angered the continent's governing body and others ahead of the new campaign when he said he would no longer recruit individuals eligible for the prestigious continental international tournament.
Unlike other major representative events, such as the European Championship and Copa America, AFCON is usually held midway through the European season, where many of its stars ply their trade.
This year's Qatar 2022 World Cup represents a break from the norm in a mid-season staging, though that was a decision dictated by the weather and the top leagues will pause for the competition.
De Laurentiis has been widely condemned for his words stating he would not bring such players to the club comments and now the continent's governing body have weighed in on the matter too.
"CAF is appalled by the irresponsible and unacceptable remarks made by Napoli President, Mr Aurelio De Laurentiis on African players and the Africa Cup of Nations," read an official statement.
"By publicly declaring that players who sign for Napoli must sign a waiver denouncing participation in the Africa Cup of Nations as a condition of employment, De Laurentiis' comments are likely to fall under Article 14 of the UEFA Disciplinary Regulations.
"CAF therefore urges UEFA to initiate disciplinary investigation against him. We have no doubt that Napoli and UEFA are as committed as CAF is to these global humanitarian objectives.
"Are we to assume that the chairman of Napoli is going to include similar restrictive conditions to players from South America, Asia and other Confederations prohibiting them from playing in their Continental competitions which are important for the development and growth of football globally?"
The next iteration of AFCON is set to be held in January 2024 in the Ivory Coast, having been postponed from June and July 2023 over weather concerns.