BackgroundCOVID-19 has caused morbidity, hospitalisation and mortality worldwide. Despite effective vaccines, there is still a need for effective treatments, especially for people in the community. Dietary supplements have long been used to treat respiratory infections, and preliminary evidence indicates some may be effective in people with COVID-19. We sought to evaluate whether a combination of vitamin C, vitamin D₃, vitamin K₂and zinc could improve overall health and decrease symptom burden in outpatients diagnosed with COVID-19.MethodsParticipants were randomised to receive either vitamin C (6 g), vitamin D₃(1000 units), vitamin K₂(240 μg) and zinc acetate (75 mg) or placebo daily for 21 days and were followed for 12 weeks. An additional loading dose of 50 000 units vitamin D₃(or placebo) was given on day one. The primary outcome was participant-reported overall health using the EuroQol Visual Assessment Scale summed over 21 days. Secondary outcomes included health status, symptom severity, symptom duration, delayed return to usual health, frequency of hospitalisation and mortality.Results90 patients (46 control, 44 treatment) were randomised. The study was stopped prematurely due to insufficient capacity for recruitment. The mean difference (control–treatment) in cumulative overall health was −37.4 (95% CI −157.2 to 82.3), p=0.53 on a scale of 0–2100. No clinically or statistically significant differences were seen in any secondary outcomes.InterpretationIn this double-blind, placebo-controlled, randomised trial of outpatients diagnosed with COVID-19, the dietary supplements vitamin C, vitamin D₃, vitamin K₂and zinc acetate showed no clinically or statistically significant effects on the documented measures of health compared with a placebo when given for 21 days. Termination due to feasibility limited our ability to demonstrate the efficacy of these supplements for COVID-19. Further research is needed to determine clinical utility.Trial registration numberNCT04780061.