The 61-year-old was confirmed as Ernesto Valverde's replacement at the start of this week and will be desperate to start with a victory over a team that sit 10th in La Liga after 19 matches of the campaign.
As it turned out, the 3-2 loss to Atletico Madrid in the Spanish Super Cup semi-final last Thursday proved to be Valverde's final game in charge. The Spaniard delivered back-to-back La Liga titles during his time in charge but has now been relieved of his duties and replaced by Setien.
The club's legendary midfielder Xavi recently revealed that he turned down the chance to take the managerial position as he felt that it was "too soon". Setien has profited to be handed the honour of leading the side, and it will be fascinating to see how the former Real Betis boss performs at Camp Nou.
It is not often that a new manager takes over a team that sit top of the table, but Barca are currently at the summit on goal difference from Real Madrid. That said, Los Blancos will have the chance to claim first spot on Saturday afternoon when they welcome Sevilla to the Bernabeu.
Setien's first two games in charge will be against Granada on Sunday night and away to Ibiza in the Copa del Rey on Wednesday before January finishes with a difficult game away to Valencia.
The Champions League will also resume next month, and the Catalan giants will travel to Napoli for the first leg of their last-16 affair on February 25 before the reverse match at Camp Nou on March 18.
Granada are the team tasked with making it an unhappy start for Barca's new boss, and the visitors are certainly capable of making it an uncomfortable 90 minutes for the Spanish champions.
Promoted back to La Liga courtesy of finishing second in the Segunda Division last season, Diego Martinez's side have enjoyed a solid campaign to date, picking up 27 points from their 19 matches to sit 10th.
El Grana, who beat Mallorca 1-0 in their last league fixture on January 5, will be looking to consolidate in the top flight, but they have not finished higher than 15th in La Liga since 1973-74 and therefore their form up until this point must be considered a success.
The fact that their top scorer in the league this season is Antonio Puertas with four is an indication of their troubles, but they have only conceded 25 times in their 19 matches which is far from a disastrous record.
Barcelona La Liga form: WWDDWD
Barcelona form (all competitions): WDDWDL
Granada La Liga form: DLWLLW
Granada form (all competitions): WLWLWW
Marc-Andre ter Stegen's knee issue has also settled, and the German is being tipped to return between the sticks for Sunday night's clash at Camp Nou.
Suarez's injury could open the door for Ansu Fati to start alongside Lionel Messi and Antoine Griezmann in attack, while there could be a midfield role for Arturo Vidal alongside Sergio Busquets and Ivan Rakitic.
Barcelona possible starting lineup:
Ter Stegen; Roberto, Pique, Lenglet, Alba; Busquets, Rakitic, Vidal; Fati, Griezmann, Messi
Granada possible starting lineup:
Silva; Sanchez, Duarte, Martinez; Diaz, Herrera, Gonalons, Neva; Puertas, Soldado, Machis
We say: Barcelona 2-0 Granada
Granada showed earlier this season that they know what it takes to overcome Barca, although it will be a different game entirely at Camp Nou. The Spanish champions have injury problems in the final third of the field but should still have too much for El Grana during the 90 minutes.