Healthy control participants had no prior history of COVID-19 and negative tests for SARS-CoV-2. Participants were assessed using three NIH-Toolbox (NIHTB) batteries for Cognition (NIHTB-CB), Emotion (NIHTB-EB) and Motor function (NIHTB-MB), as well as selected tests from the Patient-Reported Outcomes Measurement Information System (PROMIS). Each had BOLD-fMRI at 3 Tesla, during WM (N-back) tasks with increasing attentional/WM load. 169 participants were screened; 50 fulfilled the study criteria and had complete and usable datasets for this cross-sectional cohort study. 29 PCC participants were diagnosed with COVID-19 242±156 days earlier, had similar ages (42±12 vs. 41±12 years), gender proportion (65% vs. 57%), racial/ethnic distribution, handedness, education, and socioeconomic status, as the 21 uninfected healthy controls. Despite the high prevalence of memory (79%) and concentration (93%) complaints, the PCC group had similar and normal performance on the NIHTB-CB as the controls. However, PCC participants had greater brain activation than the controls across the network (p-FDR-corrected=0.003, T-max=4.17), with greater activation in the right superior frontal gyrus (p=0.009, Cohen’s-d=0.81, 95%CI [0.15-1.46]) but lesser deactivation in the default mode regions (p=0.001, d=1.03, 95%CI [0.61-1.99]). Compared to controls, PCC participants also had poorer dexterity and endurance on the NIHTB-MB, higher T-scores for negative affect and perceived stress, but lower T-scores for psychological well-being on the NIHTB-EB, as well as more pain symptoms and poorer mental and physical health on measures from PROMIS. Greater brain activation also predicted poorer scores on measures that were abnormal on the NIHTB-EB. The authors concluded that PCC participants with neuropsychiatric symptoms demonstrated compensatory neural processes with greater usage of alternate brain regions, and reorganized networks, to maintain normal performance during WM tasks. BOLD-fMRI was sensitive for detecting brain abnormalities that correlated with various quantitative neuropsychiatric symptoms.