Atalanta start Mario Pasalic, Papu Gomez and Josip Ilicic in the Champions League Round of 16, but not Pierluigi Gollini, while Valencia welcome back some star names.
It kicks off at the Mestalla, behind closed doors due to the Coronavirus outbreak, at 20.00 GMT.
La Dea won the first leg 4-1 at San Siro with a Hans Hateboer brace, Josip Ilicic and Remo Freuler on target, while Denis Cheryshev came off the bench for an away goal.
In that tie, Gian Piero Gasperini left Duvan Zapata and Luis Muriel on the bench to begin with, using the attack of Mario Pasalic, Ilicic and Gomez.
He is sticking with that system and approach, which proved so effective in the 4-1 victory.
Rafael Toloi is still out of action, so Berat Djimsiti steps in, having been injured during the warm-up back on February 19.
Another change has Pierluigi Gollini not even on the bench after dislocating his little finger, so Marco Sportiello steps in to take the gloves.
Valencia have Gabriel Paulista available again after suspension, while Alessandro Florenzi, Francis Coquelin, Kang-In Lee, Rodrigo, Kevin Gameiro and Jasper Cillessen are back in the squad.
Ezequiel Garay, Maxi Gomez, Cristiano Piccini and Manu Vallejo are still injured, but Gabriel is now suspended.
Even though this game is played behind closed doors to avoid large gatherings of people who could spread the Coronavirus, thousands still crowded together outside the Mestalla to cheer on the team, which rather defeats the object.
Valencia:Cillessen; Wass, Coquelin, Diakhaby, Gayà; Kondogbia, Soler, Parejo, Ferran Torres; Rodrigo, Gameiro
Valencia bench:Domenech, Goncalo Guedes, Cheryshev, Lee, Ruben Sobrino, Florenzi, Hugo Guillamon
Atalanta: Sportiello; Djimsiti, Caldara, Palomino; Hateboer, De Roon, Freuler, Gosens; Pasalic; Gomez, Ilicic
Atalanta bench:Rossi, Tameze, Czyborra, Muriel, Malinovskyi, Castagne, Duvan Zapata
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