COVID-19 being a rapidly evolving pandemic, early lessons from the first deaths must be learnt to help feed into the public health guidelines. This article, therefore, aims to present the first two deaths due to COVID-19 in Uganda and their public health relevance. This is a case study of the first two COVID-19 deaths reported in Uganda, and the events were prospectively documented. The first case was a 34-year-old female and support staff at a health center II. She first presented with COVID-19 like symptoms before dying on 21st July 2020. The second case was an 80 years old female, who also presented with COVID-19 like symptoms before dying on 24th July 2020. The postmortem samples of both cases were confirmed positive for COVID-19. This study identifies a need for timely identification and testing of COVID-19 suspects, strengthening of health center capacity, as well as more awareness for effective prevention and control of COVID-19.