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Mpox remains endemic in the Democratic Republic of the Congo (DRC), where co-endemic infections and non-communicable comorbidities may influence disease severity and clinical outcomes. However, data on associated factors of adverse outcomes among hospitalised adults with mpox in African settings remain limited. This study aimed to describe the clinical profile of adults hospitalised with mpox in South Kivu Province, eastern DRC, and to explore associations between selected comorbid conditions, including HIV infection, malaria, and hyperglycaemia, and mpox disease severity, mortality, and hospitalisation duration. We conducted a multicentre retrospective observational study among adults admitted to five mpox treatment centres in South Kivu Province, DRC, between January 2024 and December 2025. Demographic, clinical, and laboratory data were extracted from routine hospital registers. Mpox disease severity (available only for a subset of participants) was classified according to WHO criteria. Participants included adults with suspected, probable or laboratory-confirmed mpox according to WHO case definitions in use during the study period. In addition to mpox disease severity, outcomes of interest included in-hospital mortality and duration of hospitalisation. Multivariable regression models were used to explore associations between selected comorbidities and clinical outcomes after adjustment for age and sex. Among 652 hospitalised adults included in the analysis, the median age was 26 years (IQR 21.0-35.0), and 383/652 (58.7%) were female. Among patients with recorded severity data (n = 104), moderate or severe mpox was documented in 88/104 (84.6%) patients. Overall mortality was 14/645 (2.2%). HIV infection was identified in 5 of the 71 participants tested (7.0%). Among participants with available test results, HIV infection appeared to be associated with higher mpox severity and mortality. Increasing age, but not HIV infection, malaria, or glycaemic status, was associated with longer hospitalisation. Because laboratory investigations were performed in only a subset of participants and missing data were substantial, these findings should be interpreted cautiously and considered exploratory. Prospective studies incorporating systematic laboratory testing and standardised clinical data collection are needed to better define factors associated with severe mpox in endemic African settings.