Aim The present study aimed to evaluate the effect of quercetin in COVID-19 treatment. Methods This was a single-centre, prospective randomised controlled cohort study. Routine care versus QCB (quercetin, vitamin C, bromelain) supplementation was compared between 447 patients with at least one chronic disease and moderate-to-severe respiratory symptoms. Demographic features, signs, laboratory results and drug administration data of patients were recorded. The endpoint was that QCB supplementation was continued throughout the follow-up period from study baseline to discharge, intubation, or death. Results The most common complaints at presentation were fatigue (62.4%), cough (61.1%), anorexia (57%), thirst (53.7%), respiratory distress (51%) and chills (48.3%). The decrease in CRP, procalcitonin and ferritin levels was higher in the QCB group (all Ps were <0.05). In the QCB group, an increase in platelet and lymphocyte counts were higher (all Ps were <0.05). QCB did not reduce the risk of events during follow-up. Adjustments for statistically significant parameters, including the lung stage, use of favipiravir and presence of comorbidity did not change the results. While there was no difference between the groups in terms of event frequency, QCB group had more advanced pulmonary findings. QCB supplement is shown to have a positive effect on laboratory recovery. Conclusion We suggest that suboptimal bioavailability of QCB may explain this. So, we conclude that if a stable blood level can be achieved for QCB, it may make a difference in the treatment of COVID-19.