To determine if creatine (Cr) supplementation could influence cognitive performance and whether any changes were related to changes in prefrontal cortex (PFC) activation during such cognitive tasks, thirty (M = 11, F = 19) participants were evenly randomized to receive supplementation with Cr (CR10:10 g/day or CR20:20 g/day) or a placebo (PLA:10 g/day) for 6 weeks. Participants completed a cognitive test battery (processing speed, episodic memory, and attention) on two separate occasions prior to and following supplementation. Functional near-infrared spectroscopy (fNIRS) was used to measure PFC oxyhemoglobin (O2Hb) during the cognitive evaluation. A two-way repeated measures ANOVA was used to determine the differences between the groups and the timepoints for the cognitive performance scores and PFC O2Hb. In addition, a one-way ANOVA of % change was used to determine pre- and post-differences between the groups. Creatine (independent of dosage) had no significant effect on the measures of cognitive performance. There was a trend for decreased relative PFC O2Hb in the CR10 group versus the PLA group in the processing speed test (p = 0.06). Overall, six weeks of Cr supplementation at a moderate or high dose does not improve cognitive performance or change PFC activation in young adults.