Abstract Objective Individuals experience chronic pain differently, not only because of different clinical diagnoses, but also because of differing degrees of influence from biopsychosocial pain modulators. We aimed to cluster patients with chronic pain into distinct subgroups based on psychosocial characteristics and pain intensity, and we subsequently examined group differences in pain-related interference approximately 1 year later. Methods In this observational, longitudinal study, patients with chronic pain (n = 94) completed validated assessments of psychosocial characteristics and pain intensity at the beginning of COVID-19–related social distancing (April to June 2020). One year later (May to June 2021), patients completed a follow-up survey with assessments of pain interference, loneliness, social support, mindfulness, and optimism. Results A cluster analysis, using psychosocial factors and pain intensity, empirically produced three patient groups: 1) psychosocial predominant (PSP), characterized by high psychosocial distress and average pain intensity; 2) pain intensity predominant (PIP), characterized by average psychosocial distress and high pain intensity; and 3) less elevated symptoms (LES), characterized by low psychosocial distress and low pain intensity. At the 1-year follow-up, patients in the PSP and PIP clusters suffered greater pain interference than patients in the LES cluster, while patients in the PSP cluster also reported greater loneliness and lower mindfulness and optimism. Conclusions An empirical psychosocial-based clustering of patients identified three distinct groups that differed in pain interference. Patients with high psychosocial modulation of pain at the onset of social distancing (the PSP cluster) suffered not only greater pain interference but also greater loneliness and lower levels of mindfulness and optimism, which suggests some potential behavioral targets for this group in the future.