Abstract SARS-CoV-2 infection often involves the nervous system, leading to cognitive dysfunctions, fatigue, and many other neurological signs that are becoming increasingly recognized. Despite mild forms of the disease accounting for most cases worldwide, research on the pathophysiology driving mild COVID-19 has received little attention. In this respect, recent evidence has pointed out that around 30–40% of non-critical, mild-to-moderate severity COVID-19 survivors may display cognitive disturbances several months post-illness. Hence, the impact of COVID-19 on brain structure and function, though potential neuropathological mechanisms underpinning cognitive alterations in post-mild COVID-19 infections, remains largely unexplored. This retrospective multicenter observational cohort study, entirely based on a healthcare workers sample (n = 65; 55% females, aged 21-61), investigated the cognitive status and the structural and functional brain integrity among non-hospitalized individuals who developed mild COVID-19 symptoms during the occurrence of SARS-CoV-2 variants Alpha–to–Delta, compared with healthy controls tested before pandemic onset. All evaluations were performed at an average of 9-month follow-up post-infection period. Participants completed a comprehensive neuropsychological assessment and structural and functional MRI exams. Radiological inspection sought to detect the presence of white matter hyperintensities (WMHs) on axial fluid-attenuated inversion recovery (FLAIR) images. Global and regional gray matter (GM) integrity assessment, analyzing changes in GM volumes and cortical thinning, and functional connectivity alterations of resting-state brain networks were also conducted. Regression analyses tested the relationships between the presence of specific cognitive impairments and potential structural and functional brain findings. Our results revealed that clinical, cognitive screening and neuropsychological examinations were average between both groups, except for specific impairments related to executive functions in the mild COVID-19. Compared to healthy controls, mild COVID-19 subjects exhibited increased juxtacortical WMHs, thalamic and occipital volume loss, and diminished resting-state functional connectivity involving the left precuneus and cuneus in default-mode network and affecting right angular gyrus and left precuneus in the dorsal attentional network. Reduced thalamic volume was the only variable selected in the final model explaining the observed executive function impairment in mild COVID-19. The presence of cognitive, structural, and functional brain abnormalities over time suggests that the action of widespread neurovascular and inflammatory phenomena on the nervous system might also occur in mild forms following COVID-19 infection rather than permanent brain damage linked to the direct or indirect action of the virus. Our findings emphasize the need to pay attention to the long-term brain-related consequences of mild COVID-19 infections during the original stream.