Causes of cognitive impairment after stroke are not yet clear because a large number of sociodemographic and clinical variables complicate the understanding of the phenomenon. We aim to evaluate sociodemographic and clinical predictors of cognitive level and depression in subjects with different lesion laterality. We assessed 153 right (n = 87) and left (n = 66) unilateral first-ever stroke patients within the first year of illness with the Structured Clinical Interview for DSM-IV-Patient Edition, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the State Trait Anger Expression Inventory, the Barthel Index, and the Mini Mental State Examination (MMSE). Sociodemographic variables were also measured. Sixty-two (41 %) patients suffered from Major Depression (MDD), and 26 (17 %) suffered from Minor Depression (MIND). An univariate analysis of variance showed that MMSE scores were different throughout the groups of left and right stroke patients with MDD, MIND and without depression. Left stroke patients with MDD were more cognitively impaired than all the other groups. This result was valid after controlling for the effect of lesion location on cognitive level difference between the groups. A series of stepwise multiple regression analyses indicated that depression severity was a predictor of cognitive level and vice-versa in left hemispheric stroke patients only. Moreover, educational level in right hemispheric stroke patients and state-anger and number of regions affected in left hemispheric stroke patients were other predictors of cognitive level. The study confirms the hypothesis that predictors of cognitive level and depression severity are different in subjects with different laterality of lesion and that MDD is associated with cognitive impairment in left stroke patients.