Background: Sickle cell disease (SCD) is an inherited disorder of sickle hemoglobin affecting millions of people worldwide. Objective: The current study aimed at detecting the prevalence of MBL2 exon-1(codon 52, 54 and 57) and promoter region (-221, X/Y) genetic polymorphisms in Egyptian children with SCD to clear out its possible role as a genetic risk factor for susceptibility to venous occlusion (VOC) and/or infections. Methodology; Genotyping of exon-1 and the promoter region was done by polymerase chain reaction for fifty SCD patients and fifty healthy controls. Results; The frequency of MBL2 promotor polymorphism was 32% for the heteromutant genotype; Y/X and 8% for the homomutant genotype; X/X IN OUR patients. No statistical difference was detected between SCD patients and controls as regards the frequency of MBL2 -221Y/X genotypes. Exon-1 gene mutation in SCD patients was 18% for the A/O genotype (A/B = 8% & A/C = 10%) and 32% for the O/O genotype (C/C = 18% & C/D = 14%). O/O genotype was significantly higher in SCD patients. Mutation at codon 57 (C allele) was significantly higher in SCD patients. For SCD patients, 68% were high MBL2 expressers, while 32% were low/intermediate MBL2 expressers with no statistical difference between the two groups as regards their clinical and laboratory data. In conclusion, our study demonstrated that there was no association between MBL2 exon-1 or promoter region (-221 X/Y) genetic polymorphisms and the susceptibility to neither VOC nor infections.