Inter must recover from the shock of their first defeat and start Joao Cancelo for this trip to a Sassuolo side revitalised by Beppe Iachini.
It kicks off at 14.00 GMT, follow the build-up and action as it happens from all eight Serie A games on the LIVEBLOG.
The Nerazzurri ran into the first bump in the road last week, as a surprise 3-1 home defeat to Udinese also saw them plummet from the top of the table to third place.
Luciano Spalletti must focus his men and regain that lost momentum, but Matias Vecino is suspended, so Roberto Gagliardini steps in to midfield, leaving Marcelo Brozovic in a more advanced role.
Antonio Candreva and Ivan Perisic also support Capocannoniere Mauro Icardi, who has 17 goals in 17 games.
At left-back, Yuto Nagatomo and Davide Santon are both dropped in favour of Danilo D'Ambrosio, shuffled across so ex-Valencia man Joao Cancelo can get his first start.
Sassuolo have regained their confidence since Iachini took over from sacked Cristian Bucchi on the bench, winning two on the bounce, including a massive upset away to Sampdoria.
They are still only three points off the relegation zone and crashed out of the Coppa Italia midweek to Atalanta.
The Neroverdi have a hefty injury list, missing Stefano Sensi, Davide Biondini and Timo Letschert.
Domenico Berardi has been in dire form this season, but is a self-confessed Inter supporter who has long been linked with a move to San Siro.
Diego Falcinelli and Matteo Politano complete the trident attack.
Inter famously won this fixture 7-0 in September 2013, but they’ve met four times at the Mapei Stadium with two victories each.
Sassuolo: Consigli; Lirola, Goldaniga, Acerbi, Peluso; Missiroli, Magnanelli, Duncan; Berardi, Falcinelli, Politano
Inter: Handanovic; Joao Cancelo, Skriniar, Miranda, D'Ambrosio; Gagliardini, Borja Valero; Candreva, Brozovic, Perisic; Icardi