The hosts were put to the sword by Marseille in their first match of 2021, whereas Nantes began the Raymond Domenech era with a goalless stalemate at home to Rennes.
Montpellier are slowly drifting further and further away from the European-chasing pack and have only managed to claim a solitary point from the last 12 on offer in Ligue 1.
Manager Michel Der Zakarian was not able to bark instructions from the touchline against Marseille as he served a one-match suspension, but on the other hand, his counterpart Andre Villas-Boas made two inspired substitutions to steer Les Olympiens to victory on Wednesday evening.
The tie was delicately poised at 1-1 following goals from Nemanja Radonjic and Florent Mollet, but Villas-Boas soon introduced Dimitri Payet and Valere Germain - a move which paid dividends as both Frenchmen netted in the final 10 minutes to condemn Montpellier to their third defeat in four.
Montpellier have now dropped to ninth in the table after Angers picked up an unexpected victory at Lille, but something has to give when Les Scoistes take on sixth-placed Monaco this weekend, so Montpellier could potentially climb back up to seventh with a win if other results go their way.
However, La Paillade's record on home soil makes for bleak reading - the hosts have succumbed to defeat in five of their last six on familiar territory and have not kept a clean sheet at the Stade de la Mosson all season.
Domenech was unable to prevent Nantes' winless run stretching to nine matches in the French top flight in his inaugural game in charge, but Les Canaris nevertheless managed to prevent an in-form Rennes extending their hot streak with a goalless draw on Wednesday.
Nantes' third successive draw on home soil was certainly a respectable result given the calibre of opponent they faced, but that point was not enough to stop Domenech's men slipping further down the table after Strasbourg put five past Nimes.
Les Canaris will certainly begin to look over their shoulder as only three points separate them from 18th-placed Dijon, and basement side Nimes are the only other team in the top flight without a win to their name from their last five fixtures.
However, fellow strugglers Reims and Strasbourg both face challenging fixtures against Saint-Etienne and Lens respectively this weeken, so an unlikely win at Montpellier could propel Nantes up to 15th at the midway point of the season, but Les Canaris have lost their last three on the road.
Despite their underwhelming form this season, Nantes will be buoyed by their recent record against Montpellier, who have only managed to prevail once in their last nine meetings with Les Canaris - losing seven of them.
Montpellier HSC Ligue 1 form: LWLDLL
Nantes Ligue 1 form: LDLDLD
Defender Pedro Mendes also missed out against Marseille due to a calf problem and is unlikely to recover in time for the visit of Nantes.
The former France boss opted for a traditional 4-4-2 in his maiden match and is unlikely to switch up his approach here, although Moses Simon is a candidate to return to the left-hand side of the attack.
Montpellier HSC possible starting lineup:
Omlin; Souquet, Congre, Cozza, Ristic; Mollet, Ferri, Chotard, Dolly; Laborde, Delort
Nantes possible starting lineup:
Lafont; Corchia, Pallois, Girotto, Traore; Louza, Toure, Abeid, Simon; Kolo Muani, Coulibaly
We say: Montpellier HSC 1-0 Nantes
Montpellier simply have to arrest their worrying slump lest they risk slipping out of contention for a Europa League spot, but the losses of Savanier and Mavididi are sure to affect them in this clash. Domenech's Nantes had the bulk of the chances against Rennes but their problems in front of goal are apparent, so we can see Montpellier returning to winning ways with a slender victory here.