This systematic review and meta-analysis examines cognitive impairment in patients with Major Depressive Disorder (MDD) using the Cambridge Neuropsychological Test Automated Battery (CANTAB). The study included 33 studies with a total of 2,596 subjects, comparing MDD patients to healthy controls. Overall, MDD patients showed moderate cognitive deficits (SMD, -0.39 [95% CI, -0.47 to -0.31]) in executive function, memory, and attention, but not in reaction time. Subgroup analyses revealed that unmedicated MDD patients had small cognitive deficits (SMD, -0.19 [95% CI, -0.37 to -0.00]), while treatment-resistant depression (TRD) patients and older adults with MDD had moderate to large deficits (SMD, -0.56 [95% CI, -0.78 to -0.34] and SMD, -0.51 [95% CI, -0.66 to -0.36], respectively). The study highlights the importance of addressing cognitive impairment in MDD, as it can persist in remission or lead to neurodegenerative disorders.This systematic review and meta-analysis examines cognitive impairment in patients with Major Depressive Disorder (MDD) using the Cambridge Neuropsychological Test Automated Battery (CANTAB). The study included 33 studies with a total of 2,596 subjects, comparing MDD patients to healthy controls. Overall, MDD patients showed moderate cognitive deficits (SMD, -0.39 [95% CI, -0.47 to -0.31]) in executive function, memory, and attention, but not in reaction time. Subgroup analyses revealed that unmedicated MDD patients had small cognitive deficits (SMD, -0.19 [95% CI, -0.37 to -0.00]), while treatment-resistant depression (TRD) patients and older adults with MDD had moderate to large deficits (SMD, -0.56 [95% CI, -0.78 to -0.34] and SMD, -0.51 [95% CI, -0.66 to -0.36], respectively). The study highlights the importance of addressing cognitive impairment in MDD, as it can persist in remission or lead to neurodegenerative disorders.