Background: Chronic kidney disease (CKD) and its advanced form, end-stage kidney disease (ESKD), disrupt male reproductive capacity, largely due to endocrine disturbances and impaired sperm production. Kidney transplantation (KTx) may reverse these effects by normalizing kidney function and recalibrating the hypothalamic-pituitary-gonadal (HPG) axis. Here, we report the first known case of natural conception in a male with ESKD and non-obstructive azoospermia (NOA) after KTx. Case Description: A 32-year-old man experienced reduced sexual desire, mild erectile dysfunction, and infertility for four years. Workup revealed stage 3 CKD from chronic glomerulonephritis and hypertension, later advancing to ESKD, along with NOA confirmed by two semen analyses. Choosing KTx over prompt surgical sperm extraction, he achieved normalized renal function and partial endocrine recovery by 3 months post-transplant. Semen analysis confirmed restored sperm production, leading to a spontaneous pregnancy, which unfortunately ended in a miscarriage at 7 weeks. Conclusions: This case underscores the possibility of fertility restoration in azoospermic men with ESKD after KTx. Despite challenges such as sperm quality issues and immunosuppressive drugs potentially affecting outcomes, KTx appears to enhance sexual function and sperm production, providing a promising fertility option for ESKD patients. Additional reports are essential to elucidate treatment strategies and the long-term impacts of immunosuppressive agents on male reproductive health. © AME Publishing Company.