Aim: to determine the association between clinical laboratory parameters, the production of cytokines (IL-17A, -23, -33, -35), and specific IgM and IgG in the serum of patients with Lyme borreliosis without erythema migrans. Patients and Methods: complete blood count, the concentrations of IL-17A, -23, -33, -35, and the levels of specific IgM and IgG were measured during acute infection and convalescence (n=30). The control group included age- and sex-matched healthy individuals (n=30). Statistical analysis was performed using the StatSoft Statistica v 10.0 software (parametric and non-parametric methods and multifactorial analysis, i.e., principal component analysis). Results: most (80%) patients with Lyme borreliosis without erythema migrans are the people of working age. In most patients, the combination of the specific antibodies against Borrelia afzelii and Borrelia garinii (76.7%) and severe intoxication and inflammatory process (100%) were detected. Moderate and severe disease associated with meningism was diagnosed in 90% and 10%, respectively. The mean duration of hectic period was 8.3±1.27 days. Abnormal ECG was reported in 40% of patients, i.e., conduction abnormalities in 20%, sinus bradycardia in 16.7%,and sinus tachycardia in 3.3%. The clinical laboratory signs of hepatitis without jaundice were identified in 26.7%. During treatment, the significant reduction in band and segmented neutrophil counts as well as the significant increase in platelet count were revealed compared to these parameters at admission. Abnormal cytokine levels (i.e., the increase in IL-17A, -23, -33 and the deficiency of IL-35) were detected. Conclusions: multifactorial analysis has demonstrated that the severity of immunological abnormalities in patients with Lyme borreliosis without erythema migrans is associated with fever, cardiac and liver disorders, the high levels of IL-23 and IL-33, and the lack of IL-35 and specific IgM and IgG. KEYWORDS: tick-borne borreliosis, Lyme disease without erythema migrans, clinical laboratory signs, cytokines, specific antibodies, multifactorial analysis, principal component analysis. FOR CITATION: Sapozhnikova V.V., Bondarenko A.L. Multifactorial analysis of clinical laboratory signs, the levels of IL-17A, IL-23, IL-33, IL-35, and specific antibodies in the serum of patients with Lyme borreliosis without erythema migrans. Russian Medical Inquiry. 2020;4(11):676–681. DOI: 10.32364/2587-6821-2020-4-11-676-681.