In most cases, the diagnosis of lupus nephritis involves the presence of certain antibodies, such as anti-nuclear antibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) antibodies. These antibodies are highly specific markers for systemic lupus erythematosus (SLE) and are commonly used in the diagnosis and monitoring of patients. However, in some unusual cases, patients with lupus nephritis may exhibit negative results for ANA and anti-dsDNA antibodies. This presents a diagnostic challenge, as these antibodies are typically considered crucial for the identification of lupus nephritis. Kidney biopsy is one of the criteria for diagnosing SLE, according to the 2019 EULAR/ACR classification algorithm. In this report, we present the case of a lupus nephritis patient with a kidney biopsy result showing lupus nephritis class II, but negative ANA and anti-dsDNA. A 23-year-old woman presented with a complaint of butterfly rash, joint pain, fatigue, hair loss, and mouth sores. Laboratory results showed a negative ANA and negative anti-dsDNA antibodies. The patient was diagnosed clinically with SLE and received treatment with hydroxychloroquine (HCQ), mycophenolic acid, and methylprednisolone. After 1 year of treatment, the patient was declared to be in remission. Patient became pregnant, mycophenolic acid therapy was discontinued and replaced with azathioprine. After giving birth, the patient experienced generalized body swelling and foamy urine. A kidney biopsy was performed with the following result: focal mesangial proliferative glomerulonephritis, consistent with lupus nephritis class II. The modified NIH activity index was 3/24, and the chronicity index was 4/12. Immunofluorescence microscopy showed immune deposits positive for IgM, but no immune deposits were found for IgG, IgA, C3, and C1q. Fibrinogen accentuated the vessel walls. Increased dose of mycophenolic acid, methylprednisolone, and HCQ was given. After 1 month, the patient experienced worsening body swelling and shortness of breath. Hemodialysis therapy was performed due to acute lung edema and uremic syndrome.