Background Evidence on the risk factors for COVID-19 hospitalization, mortality, hospital stay and cost of treatment in the African context is limited. This study aims to quantify the impact of known risk factors on these outcomes in a large South African private health insured population. Methods and findings This is a cross sectional analytic study based on the analysis of the records of members belonging to health insurances administered by Discovery Health (PTY) Ltd. Demographic data for 188,292 members who tested COVID-19 positive over the period 1 March 2020–28 February 2021 and the hospitalization data for these members up until 30 June 2021 were extracted. Logistic regression models were used for hospitalization and death outcomes, while length of hospital stay and (log) cost per patient were modelled by negative binominal and linear regression models. We accounted for potential differences in the population served and the quality of care within different geographic health regions by including the health district as a random effect. Overall hospitalization and mortality risk was 18.8% and 3.3% respectively. Those aged 65+ years, those with 3 or more comorbidities and males had the highest hospitalization and mortality risks and the longest and costliest hospital stays. Hospitalization and mortality risks were higher in wave 2 than in wave 1. Hospital and mortality risk varied across provinces, even after controlling for important predictors. Hospitalization and mortality risks were the highest for diabetes alone or in combination with hypertension, hypercholesterolemia and ischemic heart disease. Conclusions These findings can assist in developing better risk mitigation and management strategies. It can also allow for better resource allocation and prioritization planning as health systems struggle to meet the increased care demands resulting from the pandemic while having to deal with these in an ever-more resource constrained environment.