Decreased expression of the TCR ζ-chain has been reported in several autoimmune and inflammatory diseases. Recent evidence suggests that this deficiency may be due to polymorphisms in the CD247 gene. A total 52 patients with systemic lupus erythematosus (SLE) and 95 healthy controls of Bulgarian ethnicity were genotyped for 837C>G, rs1052230, 844A>T, and rs1052231 using a TaqMan genotyping assay. None of the two polymorphisms appeared associated with the diseases. On the other hand, we have found that the -837GG genotype and the G allele were associated with hematological disease. The -844AA genotype and the A allele appeared associated with the hematological disease as well. The -843AA genotype and the A allele were found to be associated with antinuclear antibody (ANA) tests and immunological disease. An association was found between the -837G allele and arthritis. The AG haplotype was found to be associated with hematological disease, ANA, and immunological disease. Our preliminary data confirm the previous findings that the CD247 polymorphisms are mainly associated with the clinical outcome of the disease and less with susceptibility.