Henrikh Mkhitaryan and Jordan Veretout make their Roma debuts, while Sassuolo start Vlad Chiriches and Gregoire Defrel.
It kicks off at 17.00 UK time (16.00 GMT), follow all the action as it happens on the LIVEBLOG.
The Giallorossi are still looking for their first win of the season after a 3-3 draw with Genoa and 1-1 result against rivals Lazio.
Coach Paulo Fonseca has new options at his disposal today, as Mkhitaryan arrived on loan from Arsenal on transfer deadline day and is immediately throw into the starting XI for what appears to be a 4-2-3-1 formation.
Veretout also arrived from Fiorentina in a deal worth €17m plus bonuses and makes his debut, but Nicolò Zaniolo drops to the bench.
Cengiz Under, Diego Perotti, Davide Zappacosta and Chris Smalling are all on the treatment table.
Gianluca Mancini is chosen instead of Juan Jesus for the centre-back role, while Bryan Cristante and Justin Kluivert are in the line-up supporting Edin Dzeko.
Sassuolo have to do without Rogerio and Francesco Magnanelli, but ex-Roma striker Defrel immediately gets to face his former teammates at the Stadio Olimpico.
He takes the place of Jeremie Boga in a trident attack with Domenico Berardi and Ciccio Caputo.
Veteran defender Chiriches also starts for his Sassuolo debut after the move from Napoli.
Roma: Pau Lopez; Florenzi, Fazio, Mancini, Kolarov; Veretout, Cristante; Mkhitaryan, Pellegrini, Kluivert; Dzeko
Roma bench: Fuzato, Mirante, Juan Jesus, Cetin, Santon, Kalinic, Zaniolo, Pastore, Spinazzola, Diawara, Antonucci
Sassuolo: Consigli; Marlon, Chiriches, Ferrari, Peluso; Duncan, Obiang, Locatelli; Berardi, Caputo, Defrel
Sassuolo bench: Pegolo, Russo, Boga, Muldur, Raspadori, Romagna, Toljan, Traore, Tripaldelli, Mazzitelli, Ghion, Kyriakopoulos
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