Objective Despite the increasing disease burden, there is a dearth of context-specific evidence on the risk factors for COVID-19 positivity and subsequent death in Nigeria. Thus, the study objective was to identify context-specific factors associated with testing positive for COVID-19 and fatality in Nigeria.Design Retrospective cohort study.Setting COVID-19 surveillance and laboratory centres in 36 states and the Federal Capital Territory reporting data to the Nigeria Centre for Disease Control.Participants Individuals who were investigated for SARS-CoV-2 using real-time PCR testing during the study period 27 February–8 June 2020.Methods COVID-19 positivity and subsequent mortality. Multivariable logistic regression analyses were performed to identify factors independently associated with both outcome variables, and findings are presented as adjusted ORs (aORs) and 95% CIs.Results A total of 36 496 patients were tested for COVID-19, with 10 517 confirmed cases. Of 3215 confirmed cases with available clinical outcomes, 295 died. Factors independently associated with COVID-19 positivity were older age (p value for trend<0.0001), male sex (aOR 1.11, 95% CI 1.04 to 1.18) and the following presenting symptoms: cough (aOR 1.23, 95% CI 1.13 to 1.32), fever (aOR 1.45, 95% CI 1.45 to 1.71), loss of smell (aOR 7.78, 95% CI 5.19 to 11.66) and loss of taste (aOR 2.50, 95% CI 1.60 to 3.90). An increased risk of mortality following COVID-19 was observed in those aged ≥51 years, patients in farming occupation (aOR 7.56, 95% CI 1.70 to 33.53) and those presenting with cough (aOR 2.06, 95% CI 1.41 to 3.01), breathing difficulties (aOR 5.68, 95% CI 3.77 to 8.58) and vomiting (aOR 2.54, 95% CI 1.33 to 4.84).Conclusion The significant risk factors associated with COVID-19 positivity and subsequent mortality in the Nigerian population are similar to those reported in studies from other countries and should guide clinical decisions for COVID-19 testing and specialist care referrals.