Psychological stress is a suggested risk factor of metabolic disorders, but molecular mediators are not well understood. We investigated the association between the metabolic profiles of fasting plasma and the improvement of psychological well-being using non-targeted liquid chromatography-mass spectrometry (LC-MS) platform. The metabolic profiles of volunteers participating in the face-to-face intervention group (n = 60) in a randomised lifestyle intervention were compared to ones of controls (n = 64) between baseline and 36-week follow-up. Despite modest differences in metabolic profile between groups, we found associations between phosphatidylcholines (PCs) and several parameters indicating stress, adiposity, relaxation, and recovery. The relief of heart-rate-variability-based stress had positive, while improved indices of recovery and relaxation in the intervention group had an inverse association with the reduction of e.g. lysophosphatidylcholines (LPC). Interleukin-1 receptor antagonist and adiposity correlated positively with the suppressed PCs and negatively with the elevated plasmalogens PC(P-18:0/22:6) and PC(P-18:0/20:4). Also, we found changes in an unknown class of lipids over time regardless of the intervention groups, which also correlated with physiological and psychological markers of stress. The associations between lipid changes with some markers of psychological wellbeing and body composition may suggest the involvement of these lipids in the shared mechanisms between psychological and metabolic health.