Objective To investigate the current status and influencing factors of decision fatigue in caregivers of children with acute leukemia, and to provide a reference for developing systemic targeted interventions. Methods The caregiver-related data were collected in the cross-sectional survey (n=209) using the general data questionnaire, the Decision Fatigue Scale (DFS), the General Self-Efficacy Scale (GSES), the Zarit Caregiver Burden Interview (ZBI), as well as the Hospital Anxiety and Depression (HAD) Scale. The influencing factors of caregiver fatigue were explored. Results The caregivers scored (13.65±4.50) points in decision fatigue, (22.90±5.88) points in self-efficacy, (36.05±11.94) points in caregiving burden, 8.00（4.00，11.00） points in anxiety, and 7.00（4.00，9.00） points in depression. Multiple linear regression analysis showed that disease risk category of the child, the number of co-caregivers, self-efficacy, and caregiver burden were influencing factors of decision fatigue in caregivers of children with leukemia （all P<0.05）. Conclusion Decision fatigue in caregivers of children with leukemia was at a medium level. Healthcare professionals should focus on caregivers whose child was in a high risk category, who had fewer co-caregivers, who had low self-efficacy and who had high caregiving burden, and take such measure to reduce their decision fatigue as increasing caregivers′ self-efficacy and reducing their caregiving burden.