Precis: Cognitive impairment in multiple domains was observed in primary open angle glaucoma patients as compared with age and gender-matched healthy controls. Objective: Evaluation of cognitive impairment in individuals with primary open angle glaucoma (POAG). Methods: In this case-control study, individuals with POAG (cases, n=70) were compared with age-matched and sex-matched healthy individuals (controls, n=70) using detailed ophthalmological evaluation, cognitive assessment, and serum cortisol level. A multitude of tests were employed to comprehensively assess various domains of cognitive function: Addenbrooke Cognitive Examination (ACE-III; attention/orientation, memory, language, verbal fluency, and visuospatial skills), Postgraduate Institute Memory Scale (PGIMS; verbal and nonverbal memory), Wisconsin Card Sorting Test (WCST; nonverbal executive functions), Go No-Go task (GNG; inhibitory control), and Trail Making Test (TMT; attention and working memory). Results: Intraocular pressure and cup disc ratio were significantly higher (P <0.001), while retinal nerve fiber layer (RNFL) thickness and mean deviation were significantly lower in cases as compared with controls. Cases had significantly lower scores on ACE-III and PGIMS (P<0.001) and longer test completion time in TMT-A (P=0.001). The performance of cases was also significantly worse on most parameters of the WCST and GNG tasks. Serum cortisol level was significantly higher in cases (11.75 +/- 7.41 mcg/dL) compared with controls (7.93 +/- 2.39 mcg/dL; P=0.02). A significant correlation was observed between serum cortisol level and WCST correct response (P=0.04), WCST error response (P=0.002), and total time taken in TMT-A (P=0.03). Visual field mean deviation also exhibited a significant correlation with serum cortisol level (P<0.001) and total time taken on WCST (P=0.03) and TMT-A (P=0.03). Conclusions: Individuals with POAG exhibited higher cognitive impairment and raised serum cortisol levels than age-matched healthy controls. Early recognition and management of cognitive impairment are pivotal for enhancing the quality of life and implementing comprehensive glaucoma care.