The purpose of the present study was to examine the influence of an acute bout of high-intensity resistance exercise on measures of cognitive function. Ten men (Mean ± SD: age = 24.4 ± 3.2 yrs; body mass = 85.7 ± 11.8 kg; height = 1.78 ± 0.08 m; 1 repetition maximum (1RM) = 139.0 ± 24.1 kg) gave informed consent and performed a high-intensity 6 sets of 10 repetitions of barbell back squat exercise at 80% 1RM with 2 minutes rest between sets. The Automated Neuropsychological Assessment Metrics (ANAM) was completed to assess various cognitive domains during the familiarization period, immediately before, and immediately after the high-intensity resistance exercise bout. The repeated measures ANOVAs for throughput scores (r·m^-1) demonstrated significant mean differences for the Mathematical Processing task (MTH; p < 0.001, η²_p = 0.625) where post hoc pairwise comparisons demonstrated that the post-fatigue throughput (32.0 ± 8.8 r·m^-1) was significantly greater than the pre-fatigue (23.8 ± 7.4 r·m^-1, p = 0.003, d = 1.01) and the familiarization throughput (26.4 ± 5.3 r·m^-1, p = 0.024, d = 0.77). The Coded Substitution-Delay task also demonstrated significant mean differences (CDD; p = 0.027, η²_p = 0.394) with post hoc pairwise comparisons demonstrating that the post-fatigue throughput (49.3 ± 14.4 r·m^-1) was significantly less than the pre-fatigue throughput (63.2 ± 9.6 r·m^-1, p = 0.011, d = 1.14). The repeated measures ANOVAs for reaction time (ms) demonstrated significant mean differences for MTH (p < 0.001, η²_p = 0.624) where post hoc pairwise comparisons demonstrated that the post-fatigue reaction time (1885.2 ± 582.8 ms) was significantly less than the pre-fatigue (2518.2 ± 884.8 ms, p = 0.005, d = 0.85) and familiarization (2253.7 ± 567.6 ms, p = 0.009, d = 0.64) reaction times. The Go/No-Go task demonstrated significant mean differences (GNG; p = 0.031, η²_p = 0.320) with post hoc pairwise comparisons demonstrating that the post-fatigue (285.9 ± 16.3 ms) was significantly less than the pre-fatigue (298.5 ± 12.1 ms, p = 0.006, d = 0.88) reaction times. High-intensity resistance exercise may elicit domain-specific influences on cognitive function, characterized by the facilitation of simple cognitive tasks and impairments of complex cognitive tasks.

• High-intensity squat resistance exercise may elicit domain-specific influences on cognitive function.

• Tasks associated with information processing and response inhibition was exhibited improvement for simple cognitive tasks.

• Complex cognitive associated with memory and recall exhibited decrements and impairments following the high-intensity back squat protocol.

• Understanding changes in cognition under extreme physical stress is important for interpretation of physiological influences.