Introduction Shift work and demanding work schedules contribute to occupational fatigue, negatively affecting patient safety and nurses’ well-being, consequently placing nurses and patients at risk for injury and adverse health outcomes. For preventing fatigue and minimizing its negative consequences, information about its characteristics and associated factors is required. Objectives This study aimed to assess occupational fatigue “acute fatigue, chronic fatigue, and inter-shift recovery” among Saudi nurses working 8-h shifts. Further, we explored factors associated with fatigue from nurses’ perspectives. Methods We conducted a mixed-method study with a convenience sample of Saudi nurses ( N = 282) working in four public hospitals in Saudi Arabia. Data were collected using the nurses’ profile form; the occupational fatigue exhaustion recovery (OFER) scale, for relevant quantitative data; and open-ended questions for qualitative data. We used descriptive and inferential statistics for analysing the quantitative data and content analysis of the qualitative data. Results The results showed that Saudi nurses rated themselves moderately fatigued with working 8-h shifts. The inter-shift recovery subscale showed a negative correlation with chronic fatigue and acute fatigue ( r = −0.518, r = −0.356, P