BACKGROUND: Recurrent pregnancy loss (RPL), a multifactorial and complex reproductive disorder, is diagnosed when there are two or more documented back-to-back failed pregnancies. Intradermal lymphocyte therapy (ILT) emerged as a promising intervention, aiming to modulate the intricate immunological milieu implicated in RPL. This study was designed to assess the effects of ILT on pregnancy and live birth rate and also provide insight into potential immunometabolic mechanisms underlying the clinical efficacy of lymphocyte therapy in RPL. METHODS: The study included 100 patients with RPL, who received ILT (treated group, n = 50) or routine treatment (untreated group, n = 50), as well as 30 healthy women with a history of successful pregnancy as a control group. Low-dose ILT (Three injections of 20 × 10^6 PBMCs) was administered according to a standardized protocol, and flow cytometric analysis of CD39 and CD73 expression, ELISA measurement for serum levels of TNF-α, TGF-β, IL-1, and IL-10, as well as intracellular ATP and AMP using commercially available enzymatic colorimetric assay kits, were conducted. RESULTS: Pregnancy and live birth rate were significantly higher in the treated group compared with the untreated group (p < 0.001). In patients with successful pregnancy, across all measured cytokines (TNF-α, TGF-β, IL-1, and IL-10), as well as ATP/AMP ratio and CD39⁺CD73⁺ cell frequency, treated patients exhibited significant pre- to post-treatment changes, whereas routine treatment patients showed no statistically meaningful differences. After treatment, between-group differences were statistically significant across all measured outcomes, although the level of statistical significance varied across outcomes. CONCLUSION: Low-dose ILT may be associated with improved successful pregnancy and live birth rates in RPL patients. These clinical outcomes coincided with changes in purinergic signaling, inflammatory cytokines, and cellular energy status; however, formal mediation cannot be inferred from the present analysis.