Cohabitation during childhood has been described as a powerful inhibitor of later sexual interest in animals including humans (the ‘Westermarck effect’), serving as a brother–sister incest avoidance mechanism. Mound-building mice Mus spicilegus display a strong social inhibition of reproduction, responsible for the absence of reproduction in over-wintering tumuli. To better understand the mechanisms responsible for triggering reproduction in this monogamous species, we formed 100 experimental couples of juveniles (35 d) and surveyed reproduction for 45 d. As expected, very few couples reproduced, which confirms the role of social familiarity in the inhibition of reproduction. Temporary separation (1 h or 24 h) of the two partners had little effect on reproductive success. However, pairing with a new partner, with or without prior isolation, significantly triggered reproduction. Observations of the first encounter between new partners revealed more agonistic and less affiliative behaviour than in controls (reunion of familiar partners). Interestingly, when the new partner was a sibling of the previous one, the behavioural analysis revealed an intermediate level of aggression, indicating that kinship with the previous partner was perceived and had consequences on social behaviour. Mice could therefore choose a new partner based on its relatedness to the previous mate. Mutual tolerance between new partners during the dyadic encounter was negatively correlated with subsequent reproduction. These results demonstrate the paramount role of social novelty in triggering reproduction in this monogamous mouse, and suggest a link between agonistic behaviour and sexual motivation. In the field, mound-building mice may need to engage in agonistic interactions so as to overcome the long-lasting social inhibition of reproduction in overwintering mounds.