Cerebral salt wasting (CSW) is a rare cause of hypoosmolar hyponatremia usually associated with acute intracranial disease characterized by extracellular volume depletion due to inappropriate sodium wasting in the urine. We report a case of a 46-year-old male with recently diagnosed systemic lupus erythematosus (SLE) initially presenting with neurological involvement and an antiphospholipid syndrome (APS) who was admitted because of chronic asymptomatic hyponatremia previously assumed as secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH). Initial evaluation revealed a hypoosmolar hyponatremia with high urine osmolality and elevated urinary sodium concentration. Clinically, the patient's extracellular volume status was difficult to define accurately. After exclusion of other etiologies, a diagnosis of CSW was established and the patient started appropriate treatment with normalization of sodium levels. The challenge in diagnosing CSW relies on the differentiation from the SIADH, since it shares most of the laboratory features. The critical difference is the state of extracellular volume which can be difficult to access accurately in routine clinical practice. There is evidence that the fractional excretion of urate (FEUrate) can be of assistance. The relationship between SLE and hyponatremia is mostly limited to adverse pharmacological side effects, so to our knowledge, this is the first association between SLE with neurological involvement and CSW.