This study examined the effects of the time of hemodialysis (HD) on patients’ quality of life (QOL). This study included 175 HD patients (116 males, 59 females), aged 18–80 years (mean = 58.1 ± 11.3 years). Shift 1 was 7:00–11:00 AM, Shift 2 was 12:00–4:00 PM, Shift 3 was 5:00–9:00 PM, and Shift 4 was 10:00–2:00 AM (38, 38, 43, and 56 patients, respectively). Those on Shift 4 had a higher mean age compared with the other shifts, with a higher number of widowed people (8.6%). The proportions of males and females showed no significant differences among the shifts. The mean duration on dialysis was 42.1 ± 39.3 months, with a shorter duration for Shift 4. We observed the highest QOL score for the psychological and spiritual subscale, followed by the family subscale. Half the patients were dissatisfied with their jobs and had less satisfaction with their sexual life, their education, and getting a kidney transplant. We found a significant difference in overall QOL among shifts, with the greatest difference between Shifts 3 and 4. Health and functioning, psychological and spiritual, and social and economic scores were lowest in Shift 4, which was significantly different from Shift 1 and Shift 3. We found significant associations between overall QOL and general health, and the scores from different domains. Satisfaction was moderate in all groups. The study revealed poor QOL among Shift 4 patients; hence, they need more support in clinical practice guidelines.