An ex-27-week gestation female infant developed bilateral forearm nodules at 4 weeks of life during treatment for methicillin-sensitive Staphylococcus aureus bacteremia. A pure growth of Candida albicans was isolated on culture of both sterile aspiration of the forearm abscess and urine without evidence of methicillin-sensitive Staphylococcus aureus. The patient went on to develop bilateral obstructive renal fungal bezoars at 11 weeks of life. Bilateral nephrostomies were required to alleviate obstruction with the addition of local irrigation with amphotericin B deoxycholate. Two weeks later, urokinase via the nephrostomy tubes was added due to an unchanged appearance on ultrasound (US) and ongoing candiduria. A significant reduction in the size of bezoars was seen on US after 3 days. Sterilization of urine culture was achieved 7 weeks into treatment, and resolution of bezoars on US was seen 9 weeks after treatment began. No adverse events occurred from the use of local urokinase. Urokinase irrigation via nephrostomy is an effective and safe adjunctive treatment in refractory obstructive renal candidiasis in neonates.