We report on a patient who developed severe lithium-induced nephrogenic diabetes insipidus (NDI) and neurotoxicity, despite recommended serum lithium levels. Hydrochlorothiazide and indomethacin appeared effective antipolyuric drugs, which led to a normalization of serum osmolality. After re-initiating lithium therapy, with lithium levels around 0.3 mmol/l, recurrence of NDI or neurotoxicity was not observed, despite discontinuation of indomethacin and hydrochlorothiazide. Together with hypothyroidism, NDI and neurotoxicity must be considered in lethargic lithium-treated patients.