Depression is a chronic disorder that disables patients for a quality life, and also affects the lives of their loved ones. In addition to depressed mood and loss of pleasure in almost all activities, there is a significant change in appetite, sleep quality, feelings of fatigue and loss of energy, worthlessness or excessive guilt, decreased ability to concentrate and repeated thoughts of death or suicide. The prevalence of major depressive disorder in the world is growing, and it is estimated that by 2030 it would be a major cause in the global burden of the disease. Bipolar disorder as well as depression, is classified as an affective disorder and is characterized by episodic changes in feelings of elation, energy and irritability, and on the other hand, feelings of indifference, sadness and hopelessness. So far, there is much research on the association of ABO blood group systems and affective disorders that have yielded contradictory results. The aim of this study was to examine the association between ABO blood group system, bipolar disorder and depression in the Croatian population. The case-control study comparing women diagnosed with bipolar disorder or depression and the control group. Only women were studied, as they were more likely to suffer from depression, 96 patients diagnosed with bipolar disorder (n=39) or depression (n=57), and the control group consisted of 123 healthy blood donors. Genomic DNA was isolated on a QIAcube device for automatic nucleic acid isolation. Genotyping on 5 basic ABO alleles (O1, O2, A1, A2, B) and 15 ABO genotypes was performed by the in house method of allele-specific polymerase chain reaction (PCR-SSP). The association was examined at 3 levels: phenotypic, genotypic and allelic. The obtained p value determined by the χ2 test for the comparison of the ABO phenotype was 0.579, and for the distribution of the ABO allele was 0.323. Fisher's exact test was used to compare the frequency of ABO genotypes, and the determined p value was 0.599. The obtained p values are higher than the level of statistical significance, therefore the examined correlation was not determined at all three mentioned levels. The difference in the distribution of ABO blood groups between patients with bipolar disorder and those with depression was also examined, but the difference was not statistically significant (p = 1,000). The results of this study suggest that the ABO blood group system does not contribute to the development of bipolar disorder and depression. This is consistent with most conducted studies so far in the world. The research of this area of interest, should be continued on potential factors that may be involved in the disease, such as the enzyme dopamine beta hydroxylase (DBH), neurotransmitters, etc., and to include males in further research.