Rationale Several single or combined therapeutic approaches have been developed to treat addiction, however with partial efficacy in preventing relapse. Recently, the living environment has been suggested as a critical intervening factor determining the treatment outcomes. Despite accumulating evidence confirming a role of living conditions in the vulnerability to addictive behaviours, their impact on single or integrative therapeutic strategies preventing relapse is yet to be identified. Objectives Here, we explore the possible interaction between brief Environmental Enrichment (EE) exposure and acute fluoxetine administration in inhibiting sucrose-seeking behaviours, and whether this effect could be affected by living environment. Methods Social and isolated adult male C57BL/6 mice were trained to sucrose self-administration associated to a specific conditioning context (CxA), followed by a 7-day extinction in a different context (CxB). Afterwards, mice were exposed for 22 h to EE and then injected with fluoxetine (10 mg/kg, i.p.) 1 h before a CxA-induced sucrose-seeking test. Results Brief EE exposure and acute fluoxetine administration alone inhibited context-induced sucrose-seeking in both housing conditions; however, they exhibited additive properties only in social condition. Conclusions Our data show that social environment may influence the EE/fluoxetine interaction in inhibiting relapse to sucrose. These findings suggest that setting up proper living conditions to boost the efficacy of therapeutic approaches may represent a fundamental strategy to treat addiction disorders.