Detrimental mental fatigue effects on exercise performance have been documented in constant workload and time trial exercises, but effects on a maximal incremental test (MIT) remain poorly investigated. Mental fatigue-reduced exercise performance is related to an increased effort sensation, likely due to a reduced prefrontal cortex (PFC) activation and inhibited spontaneous behavior. Interestingly, only a few studies verified if centrally active compounds may mitigate such effects. For example, carbohydrate (CHO) mouth rinse potentiates exercise performance and reduces effort sensation, likely through its effects on PFC activation. However, it is unknown if this centrally mediated effect of CHO mouth rinse may mitigate mental fatigue-reduced exercise performance. After a proof-of-principle study, showing a mental fatigue-reduced MIT performance, we observed that CHO mouth rinse mitigated MIT performance reductions in mentally fatigued cyclists, regardless of PFC alterations. When compared to placebo, mentally fatigued cyclists improved MIT performance by 2.24–2.33% when rinsing their mouth with CHO during MIT. However, PFC and motor cortex activation during MIT in both CHO and placebo mouth rinses were greater than in mental fatigue. Results showed that CHO mouth rinse mitigated the mental fatigue-reduced MIT performance, but challenged the role of CHO mouth rinse on PFC and motor cortex activation.