Self-Medication (SM) involves the utilization of medicines to treat self-recognized symptoms or diseases without consultation and the irrational use of over-the-counter drugs. During the COVID-19 pandemic, the lack of definitive treatment led to increased SM. We aimed to estimate the extent of SM for drugs used to treat COVID-19 symptoms by collecting data from pharmacy sale records. The study was conducted in Kampala, Uganda, where we extracted data from community pharmacies with functional Electronic Health Records between January 2018 and October 2021 to enable a comparison of pre-and post-COVID-19. The data included the number of clients purchasing the following drugs used to treat COVID-19 and its symptoms: Antibiotics included Azithromycin, Erythromycin, and Ciprofloxacin; Supplements included Zinc and vitamin C, while Corticosteroids included dexamethasone. A negative binomial model was used to estimate the incident rate ratios for each drug to compare the effect of COVID-19 on SM. In the pre- COVID-19 period (1st January 2018 to 11th March 2020), 19,285 customers purchased antibiotics which included; Azithromycin (n = 6077), Ciprofloxacin (n = 6066) and Erythromycin (n = 997); health supplements including Vitamin C (430) and Zinc (n = 138); and Corticosteroid including Dexamethasone (n = 5577). During the COVID-19 pandemic (from 15th March 2020 to the data extraction date in October 2021), we observed a 99% increase in clients purchasing the same drugs. The number of clients purchasing Azithromycin increased by 19.7% to 279, Ciprofloxacin reduced by 58.8% to 96 clients, and those buying Erythromycin similarly reduced by 35.8% to 492 clients. In comparison, there were increases of 170%, 181%, and 377% for Vitamin C, Zinc, and Dexamethasone, respectively. The COVID-19 pandemic underscored the extent of SM in Uganda. We recommend future studies with a representation of data from pharmacies located in rural and urban areas to further study pandemics' effect on antimicrobials prescriptions, including obtaining pharmacists' perspectives using mixed methods approaches.