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OBJECTIVE Investigation of the quality of life (QoL) of nursing staff in a Greek public hospital and its determinants. METHOD A cross-sectional study was conducted in a Greek regional public general hospital during November 2019 with a convenience sample of the nursing staff. QoL was assessed by the self-completed WHOQOL-BREF questionnaire of the World Health Organization. The independent variables were the demographic and professional characteristics of the participants (years of experience, income, shift work, etc.), and the dependent variable was QoL, according to the scores on WHOQOL-BREF. RESULTS The study population included 176 participants (response rate 88%). Cronbach's alpha coefficient was >0.7 for all the scales of the WHOQOL-BREF, indicating very good reliability of the questionnaire. The mean values on all the scales of the WHOQOL-BREF were high, indicating good to very good QoL of the nursing staff. Higher scores were recorded for social relationships, and then for physical health, mental health and environment. More hours of sleep and a higher educational level were associated with higher QoL. Participants that (a) took place in pleasurable leisure activities, (b) did not suffer from a chronic disease, (c) did not want to change their job, and (d) worked in a second job, recorded better QoL. CONCLUSIONS Various demographic and professional characteristics affect the QoL of nursing staff. Appropriate interventions should be introduced to promote the QoL of Greek nursing staff. [ABSTRACT FROM AUTHOR]