Hypoxia activates catecholamine neurons in the caudal ventrolateral medulla (CVLM). The hypothalamic paraventricular nucleus (PVN) modulates arterial chemoreflex responses and receives catecholaminergic projections from the CVLM, but it is not known whether the CVLM-PVN projection is activated by chemoreflex stimulation. We hypothesized that acute hypoxia (AH) activates PVN-projecting catecholaminergic neurons in the CVLM. Fluorogold (FG, 2%, 60-90nL) was microinjected into the PVN to retrogradely label CVLM neurons. After recovery, conscious rats underwent three hours of normoxia (21% O₂, n=4) or AH (12, 10, or 8% O₂; n=5 each group). We used Fos-immunoreactivity (IR) as an index of CVLM neuronal activation and tyrosine hydroxylase (TH)-IR to identify catecholaminergic neurons. Positively labeled neurons were counted in six caudal-rostral sections containing CVLM. Hypoxia progressively increased the number of Fos-IR CVLM cells (21%: 19 ± 6; 12%: 49 ± 2; 10%: 117 ± 8; 8%: 179 ± 7; p<0.001). Catecholaminergic cells co-labeled with Fos-IR in the CVLM were observed following 12% O₂ and further increases in severity of hypoxia caused markedly more activation. PVN-projecting CVLM cells were activated following more severe hypoxia (10% and 8% O₂). A large proportion (89 ± 3%) of all activated PVN-projecting CVLM neurons were catecholaminergic, regardless of hypoxia intensity. Data suggest that catecholaminergic, PVN-projecting CVLM neurons are particularly hypoxia-sensitive and these neurons may be important in the cardiorespiratory or neuroendocrine responses elicited by the chemoreflex.