A 67-year-old male with history of well controlled type 2 diabetes mellitus and hypertension developed acute interstitial nephritis (AIN) with nephrotic-range proteinuria during treatment with cefazolin for methicillin-sensitive Staphylococcus aureus and Group B Streptococcus (GBS) bacteremia. The patient received intravenous cefazolin 2 g every 8 h for 4 weeks prior to presentation to the emergency department with abdominal distension, nausea, and vomiting. Investigations revealed a serum ascites albumin gradient of 1.0 with total protein of 1.8 g/dL suggestive of nephrotic syndrome, which was confirmed with a spot urine protein/creatinine ratio that estimated 7.95 g of protein per day. Serum creatinine was elevated compared with baseline. Urine studies showed sterile pyuria with 3+ protein and eosinophiluria. The patient was diagnosed with AIN with nephrotic-range proteinuria associated with cefazolin use. Cefazolin was discontinued and, within a couple of days, the patient's creatinine stabilized. He was discharged with prednisone 60 mg once a day for 10 days with a taper over 2 weeks for his AIN. The patient's creatinine and proteinuria slowly decreased over the next couple of weeks, however, did not recover to baseline. A Naranjo assessment score of 6 was obtained, indicating a probable relationship between the patient's AIN with nephrotic-range proteinuria and his use of cefazolin.