Messi looked jaded in the second half of Saturday's 1-0 defeat at Atletico Madrid, having travelled back from Argentina on the Thursday following South American World Cup qualifying.
Frenkie De Jong, who has been an ever-present of late, has also been given the evening off despite Barca's growing injury list.
Gerard Pique will now be missing for perhaps the entirety of the season after the central defender suffered an ACL injury on his right knee.
Pique suffered an accidental collision with Angel Correa and the prognosis doesn't look good for the World Cup winner. What's more, Sergi Roberto tore a thigh muscle in the same match and he will be out for at least two months.
Things don't look particularly good for Barca in other positions, either, Sergio Busquets is missing for the trip to Kiev after suffering a light injury on international duty.
Ansu Fati's knee problem will keep him out until March, leaving Ronald Koeman's already-thin squad on the verge of breaking point.
Barcelona barely have a fit enough back line to field, and with De Jong rested Clement Lenglet is the only first-term centre-back which means B-team player Oscar Mingueza may be given a surprise start at the back.
Ahead of him, it may mean either Philippe Coutinho or Pedri playing in the double pivot alongside Miralem Pjanic, a position not favoured by either but needs must. But Koeman may opt to play safe and so with Carles Alena, a more natural in the position but one who has barely played at all this season.
If Alena plays, Coutinho and Pedri will take up the spots in the front four with Ousmane Dembele and Antoine Griezmann.