A 10-yr-old, captive, intact male Asian small-clawed otter (Amblonyx cinereus) with a history of bilateral nephrolithiasis was presented for acute-onset lethargy and inappetance of 5 days duration. On physical examination, the otter was about 8% dehydrated and a palpable fluid wave was present in the abdomen. An abdominal ultrasound revealed hydronephrosis of the left kidney and a hyperechoic structure present within the lumen of the left ureter, causing an obstruction. A urinalysis revealed struvite crystalluria, bacteriuria, and an elevated pH. Following 4 days of antibiotic therapy, a left ureteronephrectomy was performed. Upon opening the kidney to retrieve calculi, a large amount of purulent material was noted within the renal pelvis. To the authors' knowledge, this is the first documented case of a nephrectomy in an Asian small-clawed otter. Nephrectomy should be considered as a viable option for treatment of ureteral obstruction, hydronephrosis, or severe pyelonephritis.