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We assessed the vaccination effectiveness (VE) of a COVID-19 booster vaccine dose and the association between morbidity and absenteeism with COVID-19 booster vaccine receipt among healthcare personnel (HCP) in 2022–2023 in Greece. We followed 5752 HCP from November 14, 2022 through May 28, 2023 for episodes of absenteeism. Absenteeism for non-infectious causes, pregnancy leave, or annual leave was not recorded. Full vaccination was defined as a primary vaccination series plus one booster dose within the past six months. Multivariable regression models were used to estimate the association of full COVID-19 vaccination with the outcomes of interest. A total of 1029 episodes of absenteeism occurred during the study period (17.9 episodes per 100 HCP). The mean duration of absence per episode was 5.2 days, and the total duration of absence was 5237 days. COVID-19 was diagnosed in 736 (12.8 %) HCP, asymptomatic SARS-CoV-2 infection in 62 (1.1 %) HCP, and influenza in 95 (1.7 %) HCP. Overall, COVID-19, influenza, and asymptomatic SARS-CoV-2 infection accounted for 71.5 %, 9.2 %, and 6.0 % of episodes of absenteeism, respectively. Multivariable regression models indicated that fully vaccinated HCP were absent from work for shorter periods [adjusted odds ratio (aOR): 0.42; 95 % confidence interval (CI): 0.21–0.83], were less likely to develop COVID-19 [aOR: 0.37; 95 % CI: 0.17–0.81)], and were more likely to develop an asymptomatic SARS-CoV-2 infection (aOR: 5.90; 95 % CI: 1.27–27.45). The adjusted full VE against COVID-19 was 62.8 % (95 % CI: 18.6 %-83.0 %). COVID-19 remains a significant cause of morbidity and absenteeism among HCP. Full COVID-19 vaccination status conferred significant protection against COVID-19 and was associated with shorter periods of absence from work. [ABSTRACT FROM AUTHOR]