Globally, the coexistence of metabolic syndrome (MetS) and HIV has become an important public health problem, putting coronavirus disease 19 (COVID-19) hospitalized patients at risk for severe manifestations and higher mortality. A retrospective cross-sectional analysis was conducted to identify factors and determine their relationships with hospitalization outcomes for COVID-19 patients using secondary data from the Department of Health in Limpopo Province, South Africa. The study included 15,151 patient clinical records of laboratory-confirmed COVID-19 cases. Data on MetS was extracted in the form of a cluster of metabolic factors. These included abdominal obesity, high blood pressure, and impaired fasting glucose captured on an information sheet. Spatial distribution of mortality among patients was observed; overall (21–33%), hypertension (32–43%), diabetes (34–47%), and HIV (31–45%). A multinomial logistic regression model was applied to identify factors and determine their relationships with hospitalization outcomes for COVID-19 patients. Mortality among COVID-19 patients was associated with being older (≥50+ years), male, and HIV positive. Having hypertension and diabetes reduced the duration from admission to death. Being transferred from a primary health facility (PHC) to a referral hospital among COVID-19 patients was associated with ventilation and less chance of being transferred to another health facility when having HIV plus MetS. Patients with MetS had a higher mortality rate within seven days of hospitalization, followed by those with obesity as an individual component. MetS and its components such as hypertension, diabetes, and obesity should be considered a composite predictor of COVID-19 fatal outcomes, mostly, increased risk of mortality. The study increases our understanding of the common contributing variables to severe manifestations and a greater mortality risk among COVID-19 hospitalized patients by investigating the influence of MetS, its components, and HIV coexistence. Prevention remains the mainstay for both communicable and non-communicable diseases. The findings underscore the need for improvement of critical care resources across South Africa.