Sleep quality plays a critical role in maintaining both mental and physical health. Circadian rhythm and sleep disorders involve disruptions in the alignment between internal biological rhythms and environmental or social cues. This study aims to investigate the relationship between circadian rhythm/sleep disturbances and neurodegenerative markers in shift-working healthcare professionals. This study was conducted at Harran University Medical Faculty Hospital and included 30 night-shift healthcare workers (subject group) and 29 daytime workers (control group). Data were collected via a 25-item questionnaire on sociodemographic characteristics and work conditions, administered through face-to-face interviews. Participants also completed the Pittsburgh Sleep Quality Index (PSQI) and the Morningness-Eveningness Questionnaire (MEQ). Single morning blood samples were analyzed for neurodegenerative biomarkers (a calcium-binding protein called S100B and neuron-specific enolase, NSE), and melatonin levels were assessed from a single morning blood plasma sample. Between-group comparisons were made for questionnaire scores and biomarker levels. In the subject group, pre- and post-shift biomarker levels were also compared. The relationship between sleep quality and biomarker levels was examined. The subject group included 14 females (46.7%) and 16 males (53.3%); the control group included 15 females (51.7%) and 14 males (48.3%). The median duration of shift work was 12 h (range: 8-24). Compared to the control group, the shift workers had significantly higher PSQI scores ( = 0.002), lower MEQ scores ( = 0.003), elevated S100B levels ( = 0.003), and reduced melatonin levels ( = 0.037). Within the subject group, NSE levels were significantly higher after the shift compared to pre-shift values ( = 0.010). This study suggests that post-shift insomnia in night-shift healthcare workers is associated with elevated NSE levels, while chronic shift work is linked to increased S100B and decreased melatonin. These findings support a potential association between circadian rhythm/sleep disturbances and neurodegenerative markers. p p p p p
