Objective To establish the prevalence and risk factors for the development of suspected or confirmed coronavirus disease 2019 (COVID-19) infection among healthcare workers (HCWs) in the United Kingdom (UK). Design Cross-sectional observational study. Setting UK-based primary and secondary care. Participants HCWs aged ≥18 years working between 1 February and 25 May 2020. Main outcome measures A composite endpoint of laboratory-confirmed diagnosis of SARS-CoV-2, or self-isolation or hospitalisation due to suspected or confirmed COVID-19. Results Of 6152 eligible responses, the composite endpoint was present in 1806 (29.4%) HCWs, of whom 49 (0.8%) were hospitalised, 459 (7.5%) tested positive for SARS-CoV-2, and 1776 (28.9%) reported self-isolation. The strongest risk factor associated with the presence of the primary composite endpoint was increasing frequency of contact with suspected or confirmed COVID-19 cases without adequate personal protective equipment (PPE): ″Never″ (reference), ″Rarely″ (adjusted odds ratio 1.06, (95% confidence interval: 0.87 to 1.29)), ″Sometimes″ (1.7 (1.37 to 2.10)), ″Often″ (1.84 (1.28 to 2.63)), ″Always″ (2.93, (1.75 to 5.06)). Additionally, several comorbidities (cancer, respiratory disease, and obesity); working in a ′doctors′ role; using public transportation for work; regular contact with suspected or confirmed COVID-19 patients; and lack of PPE were also associated with the presence of the primary endpoint. 1382 (22.5%) HCWs reported lacking access to PPE items while having clinical contact with suspected or confirmed COVID-19 cases. Overall, between 11,870 and 21,158 days of self-isolation were required by the cohort, equalling approximately 71 to 127 working days lost per 1000 working days. Conclusions Suspected or confirmed COVID-19 was more common in HCWs than in the general population. Risk factors included inadequate PPE, which was reported by nearly a quarter of HCWs. Governments and policymakers must ensure adequate PPE is available as well as developing strategies to mitigate risk for high-risk HCWs during future COVID-19 waves.