Multimorbidity burden is associated with lower perceived health and life satisfaction in urban South Africa.

Multimorbidity is increasing in low- and middle-income urban settings, but its burden may be underestimated when quality of life (QoL) is summarised using a single global score. We analysed Gauteng City-Region Observatory Quality of Life Survey 7 (2023/24) data from 1782 adults in Gauteng Province, South Africa, who reported at least two clinician-diagnosed chronic conditions. Multimorbidity burden was defined as exactly two conditions versus three or more conditions. General linear models examined associations with the global QoL index and seven QoL domains, adjusting for age, sex, and socioeconomic status (SES), with false-discovery-rate correction across domains. Adjusted global QoL differed little between groups, whereas respondents with three or more conditions reported lower perceived health and life satisfaction. Exploratory SES-stratified analyses among respondents with complex multimorbidity indicated lower global QoL, service access, and life satisfaction in lower SES strata, while perceived health showed a positive but non-FDR-robust gradient. These findings suggest that domain-specific QoL indicators may reveal burdens obscured by global QoL scores. Limitations include the cross-sectional design, self-reported diagnoses, and use of a single multidomain QoL instrument; future longitudinal work should test SES as a modifier of multimorbidity-related QoL trajectories.