The epidemiological situation in Tajikistan Republic deteriorated in the 1990s, when an influx of refugees from Afghanistan resulted in mass importation of Plasmodium vivax and Plasmodium falciparum malaria to Khatlon region. The National Programme of Malaria Control was successful and malaria transmission was interrupted in 2009. Background. The aim of this study was to investigate the mechanisms of immunological response in Tajik children with tropical Plasmodium falciparum malaria. Materials and Methods. We examined 124 patients with P. falciparum malaria at the age of 6 months up to 14 years that were hospitalized in Clinical Infectious Diseases Hospital in Dushanbe city and in Regional hospital of Khatlon region in the period 2000-2007. In most cases, they were school-age children (56%). The peak incidence was recorded in July-October. Verification of the diagnosis was based on clinical, epidemiological data, and the results of blood microscopy. In all patients, along with the standard, clinical, and laboratory tests, a number of indicators of the immune status were performed that include the T-immunity, the content of serum immunoglobulins of three main classes, the level of circulating immune complexes (CIC), C3 complement, and the concentration of key serum cytokines that have been studied in the dynamics of infectious process. Finding. The study of cellular and humoral immunity in patients with Plasmodium falciparum malaria is an obvious additional criterion in assessing the severity of infection. The imbalance of cytokine profile is an important pathogenic factor in the development of severe and recurrent forms of the disease, since the formation of a defective immune response to parasitic antigens contributes to adverse outcomes. Conclusions. Plasmodium falciparum malaria was characterized by depression of cellular and humoral immunity, the degree of which depended on the severity of the pathological process. © 2019 Nighina M. Khodzhaeva et al.