Background Worldwide, the number of SARS‐CoV‐2 infections is increasing. Serological immunoglobulin tests may help to better understand the development of immune mechanisms against SARS‐CoV‐2 in COVID‐19 cases and exposed but asymptomatic individuals. The aim of this study was to investigate exposure to SARS‐CoV‐2, symptoms, and antibody responses in a large sample of healthcare workers following a COVID‐19 outbreak. Methods A COVID‐19 outbreak among staff members of a major German children's and women's hospital was followed by massive RT‐PCR SARS‐CoV‐2 tests and provided the opportunity to study symptoms, chains of infection, and SARS‐CoV‐2–specific antibody responses (IgG and IgA) by ELISA. Study participants were classified as COVID‐19 cases, and persons with close, moderate, or no exposure to SARS‐CoV‐2 in the clinical setting, respectively. Results Out of 201 study participants, 31 were COVID‐19 cases. While most study participants experienced many symptoms indicative for SARS‐CoV‐2 infection, anosmia and coughing were remarkably more frequent in COVID‐19 cases. Approximately 80% of COVID‐19 cases developed some specific antibody response (IgA and IgG) approximately 3 weeks after onset of symptoms. Subjects in the non‐COVID‐19 groups had also elevated IgG (1.8%) and IgA values (7.6%) irrespective of contact history with cases. Conclusion We found that a significant number of diseased did not develop relevant antibody responses three weeks after symptom onset. Our data also suggest that exposure to COVID‐19 positive co‐workers in a hospital setting is not leading to the development of measurable immune responses in a significant proportion of asymptomatic contact persons.