In pig production systems, weaning is a major challenge, which may affect health and welfare of piglets. Yet, large differences exist between piglets in their responses to weaning. Research efforts have been devoted to characterising early predictors of adaptation to weaning, but focused mainly on aggressive and harmful social behaviours, whereas little is known on the importance of socio-positive behaviours. Furthermore, serotonin (5-HT), a neurotransmitter involved in the regulation of social behaviours, may also be a pertinent predictor of piglets’ adaptation to social mixing. We aimed to assess whether pre-weaning social behaviour and blood 5-HT levels were associated with behavioural and physiological responses of piglets to weaning. Social behaviours (social exploration, aggression, play fight, social locomotor play) of 62 focal piglets from 12 litters were scored continuously for 8h at 42 days. At weaning (d48), focal piglets were allocated to 4 pens of approximately 30 piglets from 6 different litters. On the 2 days following weaning (d49-50), social behaviours were scored continuously and behavioural activities were scored with 6-min instantaneous scan sampling for 6h per day. Blood was sampled one week before (d41) and 24h after (d49) weaning to measure 5-HT levels and health parameters. Post-weaning data were analysed using linear mixed models including pre-weaning parameters and sex as fi xed effects, weaning weight as covariate, and pen nested within batch as random effects. Social exploration of pen mates represented 57% and 77% of all social interactions one week before and directly after weaning, respectively. Social play was not observed on the 2 days following weaning. Exploration of pen mates one week before weaning was positively associated with exploration of pen mates (p = 0.03) and time spent active (p = 0.05) after weaning, while social locomotor play before weaning was positively associated with time spent walking after weaning (p = 0.008). Blood 5-HT levels before weaning were negatively associated with aggression (p = 0.05) and positively associated with blood 5-HT levels (p = 0.003), lymphocyte-to-neutrophil ratio (p = 0.04), and growth (p = 0.004) after weaning. A variety of pre-weaning parameters infl uenced oxidative status after weaning, with post-weaning hydroperoxide levels being associated positively with preweaning social locomotor play (p = 0.006) and negatively with pre-weaning blood 5-HT levels (p = 0.003). In conclusion, our findings suggest that pre-weaning socio-positive behaviours and blood 5-HT levels may be relevant predictors of piglets’ adaptation to weaning stress and deserve more research attention.