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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks on cruise ships have rarely been investigated. In early 2022, we were informed about a SARS-CoV-2 outbreak on a cruise ship calling Port of Hamburg after 10 infections among crew members were detected. We conducted an outbreak investigation in collaboration between ship owners, the ship physician and Hamburg's Institute for Hygiene and Environment, to identify risk factors and to achieve containment. The aim was to identify risk factors for SARS-CoV-2 infection and SARS-CoV-2 variants in a cohort of 165 crew members., Materials and Methods: For this purpose, we collected data on age, sex, nationality, boarding-time, cabin use (single/shared), work place, and vaccination status of the study participants. Cases were defined as individuals who tested SARS-CoV-2 positive at least once in daily screenings during the outbreak period (10 days) by polymerase chain reaction or antigen test. We investigated risk factors for infection by descriptive, univariable and multivariable analysis. We performed whole genome sequencing to identify SARS-CoV-2 variants., Results: We verified 103 SARS-CoV-2 positive cases (attack rate [AR] 62.4%); 39/41 sequenced samples were BA.2.3 Omicron subtype, one BA.1 and one BA.1.1. Among boostered crew members, AR was 38% vs. 65% among those vaccinated once or twice. Among those who stayed < 30 days on board, AR was 31% vs. 72% among those staying on board longer. Among Europeans, the AR was 53% vs. 71% in non- -Europeans. Adjusting for age and sex, cases were more likely to have received no booster vaccine (odds ratio [OR]: 2.66, 95% confidence interval [CI]: 0.99-7.13), to have spent more time on board (≥ 30 days, OR: 6.36, 95% CI: 2.81-14.40 vs. < 30 days) and to have a non-European nationality (OR: 2.14, 95% CI: 1.08-4.27). The outbreak stopped shortly after offboard isolation of cases., Conclusions: This investigation confirms the importance of a booster vaccine against COVID-19. Longer stays onboard could facilitate social mixing. Further studies could investigate the impact of social, cultural/ behavioural patterns and public health access on the infection risk. Physical distancing together with screening and isolation can contain SARS-CoV-2 outbreaks on cruise ships.