Background COVID-19 mitigation strategies have been challenging to implement in resource-limited settings due to the potential for widespread disruption to social and economic well-being. Here we predict the clinical severity of COVID-19 in Malawi, quantifying the potential impact of intervention strategies and increases in health system capacity. Methods The infection fatality ratios (IFR) were predicted by adjusting reported IFR for China accounting for demography, the current prevalence of comorbidities and health system capacity. These estimates were input into an age-structured deterministic model, which simulated the epidemic trajectory with non-pharmaceutical interventions and increases in health system capacity. Findings The predicted population-level IFR in Malawi, adjusted for age and comorbidity prevalence, is lower than estimated for China (0.26%, 95% uncertainty interval [UI] 0.12 – 0.69%, compared with 0.60%, 95% CI 0.4% – 1.3% in China), however the health system constraints increase the predicted IFR to 0.83%, 95% UI 0.49% – 1.39%. The interventions implemented in January 2021 could potentially avert 54,400 deaths (95% UI 26,900 – 97,300) over the course of the epidemic compared with an unmitigated outbreak. Enhanced shielding of people aged ≥ 60 years could avert a further 40,200 deaths (95% UI 25,300 – 69,700) and halve ICU admissions at the peak of the outbreak. A novel therapeutic agent, which reduces mortality by 0.65 and 0.8 for severe and critical cases respectively, in combination with increasing hospital capacity could reduce projected mortality to 2.5 deaths per 1,000 population (95% UI 1.9 – 3.6). Conclusion We find the interventions currently used in Malawi are unlikely to effectively prevent SARS-CoV-2 transmission but will have a significant impact on mortality. Increases in health system capacity and the introduction of novel therapeutics are likely to further reduce the projected numbers of deaths.