Catechol-O-methyltransferase (COMT) is an enzyme responsible for the metabolism of various catecholamines, such as neurotransmitter dopamine. It is encoded by the COMT gene, that contains numerous polymorphisms, some of which affect expression and activity of the enzyme, thereby modulating the concentration of catecholamine neurotransmitters in the synapse. Numerous studies have suggested the role of dopamine neurotransmission in the pathogenesis of depression and schizophrenia. Depressive symptoms, although rarely explored and with undetermined biological background, are very common in schizophrenia and are associated with poorer therapeutic outcomes and lower quality of life, higher comorbidity, poor work and psychosocial functioning, and an increased risk of relapse and suicide. Due to the lack of data in previous studies, the aim of this study was to determine whether there is an association between rs4680 and rs4818 COMT polymorphisms and depressive symptoms in patients with schizophrenia. Genotyping of researched polymorphisms and the PANSS-D and CDSS scales were used to assess depressive symptoms in patients with schizophrenia. Results demonstrated that the depressive symptom Early awakening was associated with rs4680 AA genotype, whereas depressive symptom Feeling of guilt was associated with rs4818 genotype CG in subjects with schizophrenia. The haplotype analysis revealed that rs4680 and rs4818 polymorphisms are in linkage disequilibrium and therefore probaby inherited in the haploblock. The CG haplotype was significantly more frequent in schizophrenia patients than in control subjects.