Fatigue affects between 42% and 89% of end-stage kidney disease (ESKD) patients, with significant repercussions on quality of life and clinical outcomes. Fatigue management revolves around pharmacotherapy or exercise, which have only modest and short-term improvements. The aim of this systematic review was to investigate whether social-psychological interventions are effective at reducing fatigue in ESKD. Databases were searched to identify randomized controlled trials (RCTs) and quasi-RCTs that determined the effect of social-psychological interventions on fatigue (primary or secondary outcome), in the renal patient population. A meta-analysis was conducted. Sixteen RCTs (N = 1536) were included, predominantly among dialysis patients. Fatigue was a primary outcome in only two studies. The meta-analytic findings showed a significant improvement in fatigue following social-psychological interventions (standardised mean difference, SMD = 0.37, p = .001; 95% CI 0.15 to 0.59, I-2 = 69.1%, p < .001). There was evidence for greater effectiveness of interventions including stress-management/relaxation techniques, evaluated among fatigued samples meeting diagnostic thresholds, against passive/non-active comparison groups. The studies were generally of poor quality, with high heterogeneity, particularly with the number of sessions ranging from 2 to 96. Development and evaluation of a fatigue-specific social-psychological intervention is warranted in this setting.