Cole faces at least two weeks out after picking up a hamstring injury in the first half of Easter Monday's FA Cup win over Manchester United so his replacement will start from the off at Stamford Bridge.
Centre-back Gary Cahill is still out a knee injury and is also likely to miss next week's return leg in Russia.
Rafa Benitez is likely to recall the experienced John Terry and Frank Lampard to his starting line-up, while Fernando Torres will lead the line with Demba Ba ineligible.
Rubin, seeking a Europa tonic after an under-par domestic campaign that sees them six-points adrift of a Champions League spot, will be without injured duo Alexander Ryazantsev and Yann M'Vila.
Midfielder Alan Kasaevis is doubtful after missing a 2-0 win over Lokomotiv Moscow last time out but Bibras Natkho, impressive for Israel during their international matches against Portugal and Northern Ireland, was on the scoresheet in that game and is fit to face the Londoners.
"We got probably the toughest opponent we could get," said Rubin manager Kurban Berdyev. "However, for us it will become just an extra motivating factor that will make this tie more attractive."