Background: Healthcare workers (HCW) are believed to be at increased risk of SARS-CoV-2 infection. The extent of that increased risk compared to the general population and the groups most at risk have not been extensively studied. It is also not known to what extent the natural production of antibodies to SARS-CoV-2 is protective against re-infection.Methods: A prospective observational study of health and social care workers in NHS Tayside (Scotland, UK) from May to September 2020. The Siemens SARS-CoV-2 total antibody assay was used to establish seroprevalence in this cohort. Controls, matched for age and sex to the general Tayside population, were studied for comparison. New infections post antibody testing were recorded to determine if the presence of SARS-CoV-2 antibodies protect against re-infection.Results: A total of 2063 health and social care workers were recruited for this study. 300 HCW had a positive antibody test (14.5%). 11/231 control sera tested positive (4.8%). HCW therefore had an increased likelihood of a positive test (Odds ratio 3.4 95% CI 1.85-6.16, pConclusion: In this study, HCW were three times more likely to test positive for SARS-CoV-2 than the general population. Almost all of the infected individuals developed an antibody response and this was 85% effective in protecting against re-infection with SARS-CoV-2.Funding Statement: NHS Tayside COVID-19 Research Fund, JDC is supported by the British Lung Foundation Chair of Respiratory Research.Declaration of Interests: JDC reports grants and personal fees from GlaxoSmithKline, Boehringer-Ingelheim, Astrazeneca, Pfizer, Bayer Healthcare, Grifols, Napp, Insmed and Zambon outside the submitted work; All other authors report no conflicts of interest.Ethics Approval Statement: West of Scotland Research Ethics committee, approval number 20/WS/0078.