Background Cognitive impairment (CI) occurs at a high frequency in primary antiphospholipid syndrome (PAPS). Its psychosocial-related factors are of interest. Objective We aimed to determine disability and perceived stress and their correlation with CI in PAPS. Methods First study phase: a longitudinal study including patients with PAPS and paired controls for cardiovascular risk factors, age, and sex, determining CI with Montreal Cognitive Assessment (MoCA) and then repeating the measurement 1 year later. Second study phase: a cross-sectional analytical study by quantification of disability with the World Health Organization Disability Assessment Schedule (WHODAS 2.0) and perceived stress with the Perceived Stress Scale (PSS-14). Descriptive statistics and Spearman correlation coefficient were used. Results Sixty-three patients with PAPS and 60 controls were studied. In PAPS, age (range, 48.0 ± 13.5 years), thrombotic artery events (TAE) (44.4%), and stroke/TIA (42.8%) were found. Disability was documented in the majority of WHODAS 2.0 domains and the total score for this was higher in participation and mobility, the stress level was normal, and 65.1% had CI. PAPS exhibited greater deterioration in the WHODAS 2.0 total score ( p .017) and the MoCA test ( p < .0001). Personal domains and the total WHODAS 2.0 score correlated inversely with MoCA. Life activities ( rho = –0.419) and self-care ( rho = –0.407) were those that correlated to the greatest degree. Stroke conferred risk for CI. Conclusions Disability in PAPS and CI are interdependent. New treatment options and neurocognitive stimulation strategies are necessary to maintain functionality and prevent further cognitive dysfunction in PAPS patients.