Background: The primary acute outcome of sickle cell disease (SCD) is a vaso-occlusive crisis (VOC) with extreme pain. More than three vaso-occlusive crisis (VOC) hospitalizations in a year increase the risk of early death. The objective of the study was to evaluate the hematological alterations in complete blood count (hemoglobin, red blood cell indices, white blood cell count, and platelets) and C-reactive protein levels during vaso-occlusive crises in patients with sickle cell anemia (HbSS) compared to a stable symptomatic state. Methodology: This study is a prospective descriptive study conducted in a hospital setting. During the period from February to June 2015, a Sudan Sickle Cell Anemia Center (SSCAC) in North Kordofan State, Sudan, treated a total of 100 patients with sickle cell anemia. Out of these patients, 74 had a vaso-occlusive crisis and 26 had a steady-state condition. All patients had measurements of their complete blood count (CBC) and C-reactive protein (CRP) levels. We calculated the average values of CBC and CRP level counts during vaso-occlusive crises and compared them to the values during steady state using independent t-tests. We analyzed the collected data using the Statistical Tool for Social Sciences (SPSS) software tool, specifically version 13. Results: The statistical analysis of the patient sample during vaso-occlusive crisis and steady state revealed that the concentration of hemoglobin (Hb) was 6.55 g/dl ± 1.3 and 9.8 g/dl ± 2.4, respectively, with a p-value of 0.000. The packed cell volume (PCV) was 20.4% ± 3.9 and 30.7% ± 7.1, respectively, with a p-value of 0.000. The red blood cell (RBC) count was 2.5×106/µl ± 0.57 and 3.9×106/µl ± 1.1, respectively, with a p-value of 0.000. A lot more white blood cells (WBC) were present in vasoocclusive than in steady state, with numbers 19.36 x 109/l ± 10.645 and 76.76 x 109/l ± 20.19, respectively, and a P-value of ≤0.000. There was a notable statistical disparity in the platelet count, with values of (357.108109/l ± 162.838) and (290.4610×9/l ± 124.40), with a P value of 0.05. In vaso-occlusive crises, the amounts of hemoglobin, packed cell volume (PCV), and red blood cells (RBCs) are lower than they are in the steady-state phase. Conversely, white blood cell (WBC) and platelet levels are much greater in patients experiencing vaso-occlusive crises compared to those in a steady state. The levels of C-reactive protein (CRP) were significantly different between patients experiencing vaso-occlusive crises and those in a stable condition.