Participants first performed a scanning task that was weak (fatigue low) or strong (fatigue high) in self-regulatory (inhibitory) demand. They then were presented a cognitive challenge that had a strong regulatory component (the Stroop color-word conflict task) or a weak regulatory component (single-digit mental multiplication) with instructions that they would avoid noise if they attained a moderate performance standard. Analysis of cardiovascular data collected during the two work periods revealed fatigue main effects for systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure. The effects reflected stronger blood pressure responses for High Fatigue participants across work periods and regardless of the character of the challenge presented in work period 2. Results conceptually replicate previous mental fatigue findings, which have shown extension of fatigue influence across cognitive performance domains. At least as importantly, they also extend those findings by showing extension across a fresh and theoretically significant cognitive performance dimension.