This time, the problem has been exacerbated by the change in staging the tournament from even to odd years, meaning there have been just 12 months between finals.
This year's tournament in South Africa, which kicks off on Saturday, features 368 players from clubs in 55 countries, showing how widely dispersed exported African players are.
There are 27 European countries represented, including Liechtenstein and Luxembourg, and clubs from Brazil, China, Japan and the United States.
The French league traditionally provides the most players, this time a total of 50, all but 15 of them from Ligue 1 clubs, who will miss key matches for the three-week tournament.
There are 15 players from the Premier League in England, 14 from the top flight in Portugal, 10 from La Liga in Spain and six from Serie A in Italy.
FIFA rules stipulate players had to be released by their clubs to prepare 14 days ahead of the competition.
Struggling French club AJ Ajaccio are paying a heavy price, losing five regulars to the Nations Cup at a time when they are attempting to stay out of the Ligue 1 relegation zone.
"It is not easy especially when you face a difficult fixture list without them," assistant coach Stephane Paganelli told the sports daily L'Equipe.
Fellow strugglers Stade Brest have lost three of their usual back four and have already moved to sign a replacement.
Herita Ilunga is a Democratic Republic of Congo international but has not been picked for the Nations Cup.
Among the high-profile players who have chosen their club over country is former South Africa captain Steven Pienaar who retired from international football last September.
Cape Verde Islands defender Ricardo also faced a difficult choice.
His national team make their debut at the Nations Cup finals after unexpected qualification but the 32-year-old centre back's club Pacos de Ferreira find themselves in unusual territory among the front-runners in the Portuguese league.
Ricardo has chosen to stay with his club for vital games over the next week as they seek a place in European club competition next season.
While his compatriots from the tiny island archipelago meet hosts South Africa in the opening game of the Nations Cup, Ricardo will be playing away at champions FC Porto.