The Inter head coach spent two years with the Genoa-based team from 2007 to 2009 - earning sixth and 13th place finishes in Serie A - before taking the reins at Napoli ahead of the 2009-10 campaign.
However, Mazzarri will put any sentimental feelings to one side at San Siro as he looks to extend his current side's unbeaten Serie A run to seven games.
Inter sit fourth in the table after 13 matches, but they were held 1-1 at lowly Bologna last time out.
That fixture at the Stadio Renato Dall'Ara saw Inter go behind after just 12 minutes courtesy of a fine effort from Panagiotis Kone, before Jonathan Moreira levelled soon after half-time.
Mazzarri could be without defender Yuto Nagatomo for visit of Sampdoria after he picked up a muscle injury at Bologna.
Sunday's match at San Siro will see ex-Inter defender Sinisa Mihajlovic take charge of his second Sampdoria game after Lorik Cana's injury-time equaliser denied him victory against another of his former clubs, Lazio, in his first fixture at the helm.
Cana's leveller denied Sampdoria their first win since a 1-0 success over Atalanta on October 26 and leaves them in 18th place, with just two wins from 13 Serie A fixtures this term.
Midfielder Nenad Krsticic was dismissed for two bookable offences against Lazio, meaning he is suspended for the trip to a ground Sampdoria have not won at since December 1996, when they secured a 4-3 victory.
The corresponding fixture last season ended 3-2 to Inter, with Diego Milito, Rodrigo Palacio and Freddy Guarin on target for the hosts while Gianni Munari and Eder replied for Sampdoria.
