Introduction Functional near infrared spectroscopy (fNIRS) is a noninvasive technique for measuring cortical brain neuroexcitation. Objective The objective of this study was to determine if fNIRS could detect differences in prefrontal cortex (PFC) neuroexcitation due to acute ON/OFF changes in sacral neuromodulation (SNM) during natural bladder filling. Study Design Female participants who had an SNM device implanted for ≥6 months underwent a 2-fill natural hydration protocol in this cross-sectional study. Continuous oxygenated hemoglobin (O2Hb) concentration was recorded using an fNIRS headcap as a measure of neuroexcitation. Sacral neuromodulation devices were acutely changed from ON to OFF and OFF to ON in 3-minute cycles. One-minute segments of fNIRS signals before and after acute modulation were selected and linear fitting was used to output slope. Two-minute control periods at a similar level of bladder sensation were used for comparison. Results Twelve women completed the study and median time from SNM implant was 13 (6, 42) months. In the left and middle PFC regions, there was a significant alteration of fNIRS slope (∆O2Hb/time) from baseline to postactivation (OFF to ON) compared to control periods. The first deactivation (ON to OFF) showed continuation of the prior fNIRS slope. The control segments showed stability of averaged O2Hb signals regardless of sensation in all brain regions. Conclusions This study indicates that fNIRS may be a useful tool to assess acute changes in neuroexcitation of the PFC in response to SNM device activation in female patients with overactive bladder. The results suggest that SNM may acutely affect the PFC during bladder filling.