Patients with sickle cell disease (SCD) tend to develop many renal abnormalities, including concentration defect, renal papillary necrosis, and glomerulopathy that often presents with proteinuria. We report a case of a patient who presented with sickle cell crisis and proteinuria. A diagnosis of SCD glomerulopathy was confirmed with renal biopsy. Treatment with angiotensin-converting enzyme inhibitor was initiated, and proteinuria rapidly reduced to 0.27 g/day. It is crucial for a clinician to recognize this important complication and take necessary precautions to delay progression to end-stage renal disease.