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A primary supraspinal structure involved in sympathetically‐mediated blood pressure control is the rostral ventrolateral medulla (RVLM). The RVLM is where the cell‐bodies of descending sympatho‐excitatory axons responsible for blood pressure control are located. The frequency through which the sympathetic nervous system modulates blood pressure has been termed the Mayer wave. The precise origin of Mayer waves has never been clearly identified. Using a rat model, our objective was to assess the causal role of the RVLM in Mayer waves, which in rats occur in the low‐frequency range of 0.4–1.0 Hz. We tested this by assessing wavelet spectrograms in response to 1) optogenetic stimulation of the RVLM, 2) orthostatic activation of the RVLM and 3) surgical disruption of descending sympatho‐excitatory pathways. We optogenetically stimulated tyrosine hydroxylase (TH)ON neurons of the RVLM in a TH:Cre rat and found increased power in the Mayer wave band of the wavelet spectrogram. When we applied an orthostatic challenge to the rodents, in order to increase baroreflex‐mediated RVLM activity, the increased power in the wavelet spectrogram was again observed. In contrast, we did not find this effect in rats after a severe T3 spinal cord contusion, which disrupts descending sympatho‐excitatory pathways. In conclusion, THON neurons in the RVLM appear to be responsible for systolic blood pressure frequency content in the Mayer wave band. Support or Funding Information Canadian Institutes of Health Research, Libin Cardiovascular Institute, Hotchkiss Brain Institute, Wings for Life, Campus Alberta Neuroscience.