Abstract Persistent somatic and neuropsychiatric symptoms have been frequently described in patients after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) even after a benign clinical course of the acute infection during the early phases of the coronavirus SARS-CoV-2 (COVID-19) pandemic and are part of Long COVID. The Omicron variant emerged in November 2021 and has rapidly become predominant due to its high infectivity and suboptimal vaccine cross-protection. The frequency of neuropsychiatric post-acute sequelae after infection with the SARS-CoV-2 Omicron and adequate vaccination status is not known. Here, we aimed to characterize post-acute symptoms in individuals with asymptomatic or mildly symptomatic breakthrough infection with SARS-CoV-2. These individuals had either proven infection with the Omicron variant (n = 157) or their infection occurred in 2022 where Omicron was the predominant variant of SARS-CoV-2 in Germany (n = 107). This mono-centric cross-sectional study was conducted at the University Medical Center Hamburg-Eppendorf between February 11, 2022, and April 11, 2022. We employed questionnaires addressing self-reported somatic symptom burden (Somatic Symptoms Scale 8 = SSS-8), and neuropsychiatric symptoms including mood (Patient Health Questionnaire 2 = PHQ-2), anxiety (Generalized Anxiety Disorder Scale 7 = GAD-7), attention (Mindful Attention Awareness Scale = MAAS), and fatigue (Fatigue Assessment Scale = FAS) in a cohort of hospital workers. Scores were compared between 175 individuals less than four weeks after positive testing for SARS-CoV-2, 88 individuals more than four weeks after positive testing, and 87 SARS-CoV-2 uninfected controls. The majority (n = 313; 89·5%) of included individuals were vaccinated at least three times. After recovery from infection, no significant difference in scores assessing neuropsychiatric and somatic symptoms were detected between the three groups (SARS-CoV-2 uninfected controls, individuals less and more than four weeks after positive testing) independent of age, sex, preconditions, and vaccination status. In addition, self-reported symptom burden did not significantly correlate with the number of vaccinations against SARS-CoV-2, time from recovery, or the number of infections. Notably, in all three groups, the mean scores for each item of our questionnaire lay below the pathological threshold. Our data shows that persistent neuropsychiatric and somatic symptoms after recovery from SARS-CoV-2 infection in fully vaccinated hospital workers do not occur more frequently than in uninfected individuals. This will guide healthcare professionals in the clinical management of patients after recovery from breakthrough infections with SARS-CoV-2.