The right-sided winger was in the starting XI, but after 26 minutes suddenly went down clutching his thigh above the knee.
He immediately called to the bench for a change and was replaced by Felipe Anderson.
The 22-year-old Dane was making his 15th appearance of the season for Lazio, in which he has contributed one assist.
Isaksen started the last three Lazio matches against Celtic, Cagliari and Genoa.
It is a new problem for Maurizio Sarri to deal with, as he already went into this match without Luis Alberto, Mattia Zaccagni, Alessio Romagnoli and Nicolò Casale.