Celiac disease (CD) is an autoimmune disorder triggered by gluten in genetically susceptible individuals, and viral infections have been proposed as potential cofactors in its pathogenesis. This study investigated the replication of SEN virus genotypes H and D in CD patients and their association with systemic cytokine levels. A total of 276 participants were enrolled, including 192 CD patients—115 on a gluten-containing diet (GCD) and 77 on a gluten-free diet (GFD)—alongside 84 healthy controls. SEN virus detection was performed using nested PCR, and serum cytokine levels (IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-γ) were quantified via ELISA. SENV-H was detected in 71.4% of CD patients on a GCD, 66.7% of those on a GFD, and only 19.0% of healthy controls. In contrast, SENV-D was found exclusively in healthy individuals (23.8%) and not in CD patients. CD patients on a GCD exhibited markedly elevated cytokine levels, particularly IL-6 (76.2 ± 12.3 pg/mL), IL-8 (112.0 ± 40.2 pg/mL), and IFN-γ (50.2 ± 15.2 pg/mL), compared to GFD patients and healthy controls. Multivariate logistic regression identified IL-1, IL-2, IL-4, IL-6, IL-8, and IL-10 as significantly associated with active disease (ORs < 1, p < 0.05). Strong to very strong positive correlations were observed between SENV-H positivity and cytokine levels, with IL-6, IL-8, and IL-1 each showing correlation coefficients around 0.99. These results suggest that SENV-H may play a role in promoting or amplifying mucosal immune responses in active CD, whereas SENV-D appears unrelated. The findings highlight a potential interaction between viral replication and immune activation in celiac disease, meriting further mechanistic investigation.