This study aimed to evaluate the association between shift work disorder and mental health in hospital‐based nurses. Staff completed an online survey comprising demographic questions, the Shift Work Disorder Questionnaire, Patient Health‐9 and the General Anxiety Disorder‐7 scale. Sick leave data were collected from archival records from the Human Resources Department. Two hundred and two nurses (95% female; age M = 35.28 years ± SD = 12) participated (42% of eligible staff). Those at high risk of shift work disorder had higher depression (M = 7.54 ± SD = 4.28 vs. M = 3.78 ± SD = 3.24; p < 0.001) and anxiety (M = 5.66 ± SD = 3.82 vs. M = 2.83 ± SD = 3.33, p < 0.001) compared to those at low risk. Linear regression models showed that being at high risk of shift work disorder was the most significant predictor of depression, explaining 18.8% of the variance in depression (R2 = 0.188, adjusted R2 = 0.184, F(1, 200) = 46.20, p < 0.001). Shift work disorder combined with the number of night shifts and alcoholic drinks on non‐work days accounted for 49.7% of the variance in anxiety scores (R2 = 0.497, adjusted R2 = 0.453, F(3, 35) = 11.51, p < 0.001). Mean sick leave in those with high risk of shift work disorder was 136.17 hr (SD = 113.11) versus 103.98 hr (SD = 94.46) in others (p = 0.057). Depression and years of shift work accounted for 18.9% of the variance in sick leave taken (R2 = 0.189, adjusted R2 = 0.180, F(2, 175) = 20.36, p < 0.001). Shift work disorder is strongly associated with depression and anxiety, providing a potential target to improve mental health in shift workers. Depression, in turn, is a significant contributing factor to sick leave.