For some, like mega-rich Paris Saint-Germain, it is simply a case of dipping into the transfer market to recruit a replacement for a player bound for the continental showcase in Gabon and Equatorial Guinea.
When Siaka Tiene was drafted into the Ivory Coast squad, PSG moved quickly to sign Barcelona's Brazilian left-back Maxwell, who made an assured debut in the leaders' 3-1 win at home to Toulouse last weekend.
Champions Lille have also been active on the transfer front, with French striker Nolan Roux poised to arrive from Brest.
Roux will cover for the absence of Senegal's Moussa Sow, although Sow has been tipped to leave for Fenerbahce after rejecting Lille's offer of a new contract.
Elsewhere, the need to balance budgets means clubs have been obliged to test the unchartered depths of their squads.
Marseille have been particularly affected by the Africa Cup of Nations, with Senegalese centre-back Souleymane Diawara and Ghana midfielder Andre Ayew leaving two gaping holes in Didier Deschamps' first XI.
OM have also lost utility player Charles Kabore (Burkina Faso) and Ayew's younger brother Jordan, but they were still able to produce a fine performance in Sunday's 2-0 defeat of Lille.
Cameroon's absence at the Cup of Nations meant Deschamps could draft Stephane Mbia into the centre of defence alongside his Cameroonian compatriot Nicolas N'Koulou, while the in-form Mathieu Valbuena deputised for the elder Ayew sibling on the left flank.
Brazilian striker Brandao has also been recalled following the end of his loan spell with Gremio after Deschamps admitted it was "the only feasible short-term solution" in attack.
Toulouse were left in a similar quandary by the departures of centre-backs Aymen Abdennour (Tunisia) and Mohamed Fofana (Mali) and Senegalese left-back Cheikh M'Bengue.
With coach Alain Casanova refusing to "buy for the sake of buying", midfielders Etienne Capoue and Franck Tabanou found themselves drawn back into defence for the trip to PSG.
"The club has made a choice to put faith in the players who are already here and it's up to them to prove they deserve that confidence," said captain Daniel Congre.
For Lyon, the loss of Burkinabe centre-back Bakary Kone has deepened a defensive injury crisis that forced them to line up at Montpellier last Saturday without six senior defenders.
Montpellier nonetheless had to scrap for their 1-0 win, but they, too, have been inconvenienced by the African tournament.
Centre-back Abdelhamid El Kaoutari (Morocco), central midfielder Jamel Saihi (Tunisia) and wide forward Souleymane Camara (Senegal) are all missing, but the biggest loss is that of Moroccan playmaker Younes Belhanda.
Belhanda's partnership with Ligue 1 top scorer Olivier Giroud has helped propel Rene Girard's side to second, but the club's reluctance to spend means France Under-21 star Remy Cabella has been given the sizeable task of stepping into Belhanda's shoes.
"The president (Louis Nicollin) was clear about (not buying new players)," said Girard earlier this month.
"We will therefore play for several weeks without four players who were important during the first half of the season.
"We'd planned for that but we hadn't planned to find ourselves in second place. We'll have to cope with this handicap by finding other solutions."
Rennes' renowned academy means they should be able to cover for the absences of forwards Jonathan Pitroipa (Burkina Faso) and Youssouf Hadji (Morocco).
Seventh-placed Saint-Etienne may struggle to keep pace with the division's leading sides, however, after losing both six-goal top scorer Pierre-Emerick Aubameyang (Gabon) and fellow forward Max Gradel (Ivory Coast).
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