Introduction: Sickle-Cell Anemia (SCA) is a genetically transmitted hemoglobinopathy, around 60 million carrier and 1,20,000 sickle cells suffer added every year in the world. In India the SCA predominantly seen in tribal region. Nutrition is a major health concern. Therefore, present study was carried out to measure serum Total protein, Albumin, Globulin, A/G Ratio, Vitamin B12, Vitamin D3, Calcium in SCA and healthy children. Aim & Objectives: To evaluate and compare biochemical parameter in SCA and healthy children’s. Material & Methods: In this comparative analytical study from total 230 subjects, 130 were SCA and 100 control were recruited after obtaining written inform consent. All subject visiting OPD between the age group of 1-12 yrs. were selected. We used whole EDTA and plain blood sample for analysis. Serum was used to measured Total Protein by Biuret method, Vitamin B12 by Electrochemilumine-scence immunoassay method, Vitamin D3 by Enzyme immunoassay competition method, Calcium by Arsenazo III method. Results: It was observed that there was no significant difference in the serum Total protein levels (p>0.05). The significant decreased levels of albumin and increased levels of globulin, A/G ratio is decreased in SCA than control. The mean of Vitamin B12 and Vitamin D3 was significantly lower in SCA when compared with control. Conclusion: In the present studynormal levels of Total protein, hypoalbuminemia and hyperglobulinemia found in SCA. Low levels of vitamin D3 and hypocobalaminemia, hypocalcaemia was observed in SCA. In toto by measuring biochemical parameter, poor nutritional status was found in SCA.