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Channel catfish (Ictalurus punctatus) are raised for aquaculture in ponds characterized by dramatic swings in dissolved oxygen concentration. If morning dissolved oxygen concentration falls below approximately 3.0 mg/L catfish consume less feed, leading to a reduction in growth and production. Although the effects of low oxygen on channel catfish appetite have been described, the underlying mechanisms responsible for those effects are unknown. Increased production of the neuropeptides corticotropin-releasing factor (CRF) and urotensin I (UI) are implicated in other fishes as neuropeptides that reduce appetite once an environmental stressor is detected. This project characterizes the hematological responses and transcriptional response of the hypothalamus to acute, chronic, and cyclical (repeating periods of hypoxia and normoxia) hypoxia. During acute (12 hours) hypoxia, venous PO2 decreased within 6 hours, coupled with an increase in hematocrit and decreased blood osmolality. These changes reversed within 12 hours after returning to normoxia but were not coupled with a change in transcription of the genes for CRF and UI. If this pattern of hypoxia and normoxia is repeated cyclically for 5 days, the same physiological responses repeat continually. During chronic hypoxia up to 5 days in duration, channel catfish have a similar hematological response, but did not recover to normoxic control values over the duration of the challenge. Likewise, no significant change in gene expression of CRF or UI were detected during chronic hypoxia. The hypothalamic transcriptome was analyzed during a 12-hour exposure to hypoxia followed by a 12-hour normoxic recovery. Across all time points, 190 genes were differentially expressed, with the greatest numbers occurring during periods of hypoxia. Differentially expressed genes were grouped into Gene Ontology biological processes and were most overrepresented by the term “response to hypoxia,†which included genes involved with angiogenesis, red blood cell production, and negative feedback to hypoxia-inducible factor proteins. Although this study did not find a change in hypothalamic transcription of CRF and UI, it did identify multiple adaptive responses that work together to reduce the severity of hypoxia along with several gene candidates for future hypoxia studies.