Fati, 21, was taken off in the first half of November's win over Nottingham Forest and has since missed Brighton's last three matches.
"It's bad news for us because he was playing better, he was understanding better the idea.
In addition to Fati, Welbeck and Enciso, Brighton, eighth in the table, are also missing Solly March from their attack through injury.
Fati joined the the south coast club on a season-long loan from Spanish champions Barça in the summer.
The Spain international burst on to the scene as a 16-year-old, but his progress since has been hit by a series of injuries.
A knee injury picked up against Real Betis in 2020 ruled him out for almost a year and a series of muscle injuries followed upon his return.
However, he went through last season without any major injury problems at Barça before joining Brighton on loan.
In 14 games in England he has scored four goals in all competitions, including three in his last seven appearances as he showed signs of adapting to De Zerbi's system.