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Lithium remains a cornerstone in the treatment of bipolar I disorder because of its well-established efficacy in reducing mood episode recurrence and suicide risk. However, its narrow therapeutic index makes patients particularly susceptible to clinically significant toxicity, especially following medication changes or drug-drug interactions. Nonsteroidal anti-inflammatory drugs (NSAIDs) are recognized to increase serum lithium concentrations by reducing renal lithium clearance, although reports involving nabumetone remain limited. We report the case of a 50-year-old woman with bipolar I disorder who had remained psychiatrically stable on chronic lithium therapy for approximately seven years before developing severe lithium toxicity following recent escalation of both lithium and nabumetone dosages. The patient presented with progressive confusion, lethargy, recurrent falls, tremor, myoclonic jerks, gait instability, generalized weakness, and altered mental status. Initial serum lithium concentration exceeded 2.9 mmol/L despite preserved renal function. Lithium and nabumetone were discontinued, aggressive intravenous fluid administration was initiated, and serial lithium concentrations were monitored. Given preserved renal function, declining serum lithium concentrations, and rapid neurologic improvement with supportive management, hemodialysis was deferred. The patient experienced progressive clinical recovery with normalization of lithium concentrations and resolution of neurologic symptoms. Lithium was cautiously reintroduced at a reduced dosage without recurrence of toxicity. Application of the Naranjo Adverse Drug Reaction Probability Scale yielded a score of 9, supporting a definite adverse drug reaction. This case highlights that severe lithium toxicity may occur despite preserved renal function following concurrent escalation of lithium and nabumetone therapy. The report emphasizes the importance of comprehensive medication reconciliation, recognition of clinically significant drug-drug interactions, close serum lithium monitoring following medication changes, and early recognition of neurologic manifestations suggestive of lithium toxicity.