Medical laboratory workers may have an increased risk of COVID-19 due to their interaction with biological samples received for testing and contamination of documents. Records of COVID-19 laboratory-confirmed positive cases within the medical laboratory service were routinely collected in the company's Occupational Health and Safety Information System (OHASIS). Surveillance data from the OHASIS system were extracted from 1 April 2020 to 31 March 2021. An epidemic curve was plotted and compared to that for the country, along with prevalence proportions and incidence rates. The odds of COVID-19 infection were categorised by job and compared to the US Occupational Risk Scores. A logistic regression model assessed the risk of COVID-19 infection per occupational group. A total of 2091 (26% of staff) COVID-19 positive cases were reported. The number of COVID-19 cases was higher in the first wave at 46% (967/2091) of cases, than in the second wave 40% (846/2091) of cases. There was no significant difference in COVID-19 prevalence between male and female employees. The job categories with the most increased risk were laboratory managers [AOR 3.2 (95%CI 1.9-5.1)] and laboratory support clerks [AOR 3.2 (95%CI 1.9-5.2)]. Our study confirms that some categories of medical laboratory staff are at increased risk for COVID-19; this is a complex interaction between workplace risk factors, community interaction, socioeconomic status, personal habits, and behaviour. Targeted interventions are recommended for high-risk groups. OHASIS has the potential to generate data for surveillance of health care workers and contribute towards a South African risk profile.