BACKGROUND: Social interactions are vital for our wellbeing, particularly during times of stress. PURPOSE: We investigated the real-time effect of social interactions on changes in stress and mood using an ecological momentary assessment approach in 732 participants during COVID-19 lockdown in spring 2020 and in a subsample of these participants (n= 281) during a further lockdown in winter 2020. METHODS: Participants reported their stress and mood in a smartphone app five times per day for seven days and indicated the nature and frequency of their recent social interactions. RESULTS: Overall, social interactions and their frequency were associated with enhanced momentary mood. In person interactions, but not those that were not in person (e.g., via audio, video, or text), were linked to lower stress, especially if they were with closer others. Individuals scoring high on trait loneliness benefited least from social interactions in terms of their momentary mood, whereas those scoring high on trait depressive symptoms benefited the most. Our key findings replicated across both lockdowns. CONCLUSIONS: This study demonstrates the benefits and limits of social interactions for improving momentary mood and stress during psychologically demanding periods and highlight how clinically relevant individual differences can modulate these effects.