Sickle cell disease (SCD) is a genetic disorder autosomal-recessive in nature effecting millions worldwide. Replacement of hydrophilic Glutamic acid (Glu) with hydrophobic Valine (Val) at the sixth position in the β-globin chainforming a mutated hemoglobin (Hb) tetramer HbS,causing distortion of the erythrocyte membrane. This leads to erythrocyte sickling. Deoxygenated HbS tetramersbind to each otherinitiating the nucleation of HbS polymer.These polymers grow & form long fibers. HbS causes cellular energetic failure, premature hemolysis, dehydration & stress. Authors, here presented Three (03) Cases of Sickle cell disease with spectrum of clinical presentation. First case was case of Sickle Cell Trait with severe anemia showing Sickle Window of 15.7 %, HbF<0.8%, HbA2- 2.6%, HbA0- 71.6%.Second case was case Co-Inheritance of Sickle cell trait and Beta Thalassemia Trait with severe anemia in obstructed labour showing S-window 16.3%, HbA2- 5.8%, HbF<0.8%, Hb A0- 67.3%. Third case was case of a Sickle cell anemiashowing S-window 73.2%, HbA2- 2.5 %, , Hb A0- 4.1 %.