The risk of SARS-CoV-2 infection is particularly high for healthcare workers during the pandemic. Home care workers visit many different households per shift. Encounters with mostly elderly patients and their relatives increase the potential for the undetected spread of SARS-CoV-2. In order to gain insight into the seroprevalence of SARS-CoV-2 antibodies and possible transmission risks in outpatient care, this follow-up study was conducted with nursing services in Hamburg. The aim was to estimate the dynamics of seroprevalence in this occupational group over a 12-month period, to identify occupation-specific risk factors, and to collect information on the vaccination status of the surveyed nursing staff. Antibody testing for SARS-CoV-2 IgG against the S1 domain (EUROIMUN Analyser I® Lübeck, Germany) was performed on participating healthcare workers with patient contact at a total of four time points within one year from July 2020 to October 2021 (baseline, follow-up after three, six and twelve months). The data were mostly analysed descriptively. Differences in IgG titres were analysed using variance analysis methods, particularly Tukey's range test. The seroprevalence was 1.2% (8/678) at baseline and 1.5% (9/581) at the three-month follow-up (T1). At the second follow-up (T2) after six months, vaccination against SARS-CoV-2 was available from January 2021 onwards. The prevalence rate of positive IgG antibodies relative to the S1 domain of the spike protein test among unvaccinated individuals was 6.5%. At (T3) after twelve months (July to October 2021), 482 participants were enrolled, and 85.7% of the workers were considered fully vaccinated at this time point, while 51 individuals were unvaccinated. The prevalence was 13.7% (7/51). In our study, a low seroprevalence was found among home care workers, which was lower than in our studies conducted in the clinical setting. Therefore, it can be assumed that the occupational risk of infection is rather low for both the nursing staff and the patients/clients cared for in the outpatient setting. The good provision of protective equipment and the high vaccination rate of the staff probably had a positive influence.