Most patients with end-stage renal disease (ESRD) benefit from a kidney transplant but there is limited information from developing countries like Uganda about the willingness of caregivers for patients with end-stage kidney disease to donate a kidney. In this cross-sectional study, we examined the magnitude and factors associated with the willingness of caregivers to donate a kidney to their patient with ESRD in Kampala, Uganda. The study was conducted at four health facilities that provide kidney dialysis in Kampala, Uganda. We used a structured questionnaire to interview caregivers for patients with ESRD. Caregivers who reported they would consider donating a kidney to a patient with ESRD were considered willing and the rest as unwilling. We summarized data using descriptive statistics and used an adjusted prevalence risk ratio (aPRR) from a generalized linear model to establish factors independently associated with willingness to donate.We enrolled 125 participants with a mean age of 32.3±9.8 years and found 68 (54.4%) participants were willing to donate a kidney for transplant. Willingness to donate a kidney was more likely among older caregivers namely those aged 25–34 years (aPRR, 1.15; 95% CI, 1.01–1.31) and ≥35 years (aPRR 1.16; 95% CI, 1.05–1.29) compared to those aged 18–24 years, females compared to males (aPRR, 1.30; 95% CI, 1.19–1.42), those with a positive attitude towards organ donation (aPRR, 1.24; 95% CI, 1.13–1.36), and when organ kidney donation was permissible by the participant’s religious faith (aPRR, 1.11; 95% CI, 1.01–1.22). Conversely, willingness to donate a kidney was less likely when the family did not approve of kidney donation (aPRR, 0.80; 95% CI, 0.71–0.90). We concluded that more than half of caregivers to patients with ESRD are willing to donate a kidney for transplant. To improve the willingness of caregivers to patients with ESRD in donating a kidney, the social, religious, and personal barriers to kidney donation may need to be addressed.