The Barcelona talent had to be substituted during Friday's (AEDT) Copa del Rey defeat to Athletic Bilbao, with the club confirming he had suffered a muscle strain to his hamstring.
It is still to be decided if the 19-year-old has surgery, but it is widely reported that he is expected to be out for at least a couple of months.
Such an absence would be a crushing blow for Fati, who appeared to be in tears as he left the pitch against Athletic, with this the latest in a series of problematic injuries.
The teenager has featured in just 10 games across all competitions this season, and he had only recently returned from a two-month hamstring injury lay-off.
Fati previously spent 10 months on the sidelines due to a serious knee injury, resuming his Barcelona career in September this season.
Prior to his return, Fati was seen as the poster boy for the post-Lionel Messi era at Camp Nou, even inheriting the Argentina great's number 10 jersey.
Despite his woes, he has vowed to keep on fighting.
Writing on his official Instagram account, Fati said: "Unfortunately, I am having to live through the worst part of football.
"But I will never give up! Thank you very much for your messages of support and love!"
It is expected to be announced on Monday whether Fati has surgery or not.