It has been reported that reactive oxygen species contribute to pathogenesis of systemic lupus erythematosus (SLE). Catalase (CAT) -330C>T transition, known also as -262C>T, generates three genotypes. The CAT -330CC genotype is associated with a significantly lower CAT expression in comparison to -330CT and -330CT genotypes. Therefore, using restriction length fragment polymorphism analysis, we compared the frequencies of CAT -330C>T polymorphic variants between SLE patients (n = 102) and controls (n = 199). We did not observe significant differences in the prevalence of CAT -330C>T polymorphic variants in SLE patients and controls. However, we found that the CAT -330CC genotype (recessive model) showed a significant association with thrombocytopenia OR = 7.314 (1.977-27.057, P = 0.0017). We also observed that the CAT -330CC genotype (recessive model) is linked with leukopenia OR = 3.232 (1.361-7.676, P = 0.0118), renal manifestations OR = 2.403 (1.085-5.321, P = 0.0471) and presence of anti-snRNP Ab OR = 4.206 (95% CI = 1.405-12.590, P = 0.0131), and anti-Scl-70 Ab, OR = 3.143 (95% CI = 1.171-8.433, P = 0.0343) in SLE patients. Our findings suggest that the CAT -330CC genotype may contribute to some clinical manifestations in patients with SLE.