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In models of altered osmolality and water balance, including two‐day salt loading and water deprivation, previous studies have suggested that intracellular redox signaling in the supraoptic nucleus (SON) contributes to the neuroendocrine response. However, the precise redox‐dependent signaling pathways and reactive oxygen species (ROS) involved in this response remain unclear. Herein, we tested the hypothesis that water deprivation increases specific ROS, particularly superoxide, and stimulates the redox‐sensitive transcription factor, nuclear factor erythroid 2‐related factor 2 (Nrf2) in the SON and that these responses are dependent on the duration of water restriction. To test this hypothesis, we used rodent models deprived of water for 24 and 48 hours (24h WD and 48h WD, respectively). We observed an increase in Nrf2 mRNA in the SON of rodents subjected to 24h WD (Control: 0.84 ± 0.08 vs 24h WD: 1 …