Abstract Background Crimean-Congo hemorrhagic fever (CCHF) virus causes severe disease in humans with a mortality reaching 30%. A CCHF outbreak took place in Albania in 2003. As in other viral hemorrhagic fevers cytokines may be involved and play a role in the pathogenesis and outcome of the disease. Objectives To investigate the levels of TNF-α, sTNF-R, IL-6 and IL-10 in serum samples obtained from laboratory confirmed CCHF cases and relate them to the severity of the disease. Study design A study population of 51 was divided into three groups: group A, consisting of PCR-positive cases; group B, consisting of PCR-negative and serology-positive cases; group C, consisting of doubly negative cases. Concentrations of serum TNF-α, sTNF-R, IL-6 and IL-10 were measured during the illness. Results High levels of all cytokines tested were present in one fatal case. Statistically significant differences between the groups were obtained for TNF-α and IL-6: TNF-α was detected in 3 cases in group A, and in none of the other groups, while IL-6 was elevated in 10/16 patients in group A, 4/9 in group B, and 4/26 in group C. sTNF-R was not significantly different for the three groups. High concentration of IL-10 was detected only in the fatal case. Conclusions TNF-α and IL-6 are the cytokines most often detected during a CCHF viral infection. TNF-α was associated with the severe form of CCHF, while IL-6 was elevated in both severe and mild cases.