Management of acute kidney injury (AKI) associated with drug-induced crystal nephropathy can be difficult, and timely diagnosis is critical to resolve this condition. We present the case of a 55-year-old woman with history of systemic lupus erythematosus (SLE), who, after treatment with trimethoprim/sulfamethoxazole (TMP/SMX) for suspected Pneumocystis jirovecii pneumonia, developed severe AKI. Automated urinary sediment initially reported hematuria, leukocyturia and "uric acid crystals". She did not have allergic symptoms, clinical manifestations of active SLE nor hyperuricemia. AKI persisted despite volume expansion with crystalloids. Due to SMX exposure, it was suspected that "uric acid crystals" could be in reality "SMX crystals", and were a possible cause of crystal nephropathy. TMP/SMX was withheld and urinary alkalization was performed, with subsequent resolution of AKI. SMX urine crystals were posteriorly confirmed by Fourier transform infrared spectroscopy.