Background: Sickle Cell Anaemia (SCA) is an inherited haemoglobin disorder characterized by shortened red cell life span and altered red blood cell parameters due to the red cell sickling, vaso-occlusion and chronic haemolysis occasioned by the disease. The occurrence of bone pain vaso-occlusive crises may further alter these parameters; an occurrence that highlights on the pathophysiology of SCA and worth noting in the management of affected patients. Aims and Objectives: This study was performed to determine the effect of bone pain vaso-occlusive crises on red blood cell parameters of SCA patients. Study Design: A longitudinal study. Settings: Fifty SCA patients receiving care at a tertiary hospital in Sokoto, Nigeria were consecutively enrolled while in their steady clinical state and followed up till when they re-presented during the bone pain vaso-occlusive crises state. Materials and Methods: Structured proforma was used for clinical data capturing while red blood cell parameters (red blood cell count (RBC), haemoglobin (Hb) concentration, haematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and red cell distribution width (RDW) were determined via automation using Nortek 3-part haematology analyser. Leishmann stained peripheral blood smears were examined to cross-check morphological details of the red blood cells. Statistics: Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 21.0 (IBM Corp, Armonk, NY, USA) and further summarized as means ± standard deviations. Comparison of means was performed using paired sample t-test and Anova as appropriate while Pearson’s test was used for correlation analysis. Results were presented in tables while statistical significance was set at p<0.05. Results: Fifty SCA patients were enrolled for the study and consisted of 26 (52%) females and 24 (48%) males. The overall mean age of the study participants was 22.82 ± 6.55 years with the minimum and maximum ages of 18 and 42 respectively. During the bone pain vaso-occlusive crises, 14 (28%), 21 (42%) and 15 (30%) of the patients had mild, moderate and severe bone pains respectively. The red blood cell parameters during the steady and bone pain crises states were RBC count (2.87±0.69 vs. 2.93±0.83; p=0.675); HCT (24.33±5.01 vs. .37±5.61; p=0.373); Hb concentration (8.34±1.53 vs. 7.99±1.54; p=0.228); MCV (87.87±9.13 vs. 82.59±14.64; p=0.021); MCH (29.76±5.61 vs. 30.48±13.54; p =0.729); MCHC (32.89±4.76 vs. 32.10±3.75; p=0.394) and RDW-CV (19.30±6.58 vs. 19.59±5.27; p=0.829) respectively. During bone pain vaso-occlusive crises, the red blood cell parameters based on mild, moderate and severe pains were RBC count (2.82±0.88 vs. 2.78±0.57 and 3.06±0.65; p=0.472); HCT (24.29±6.37 vs. 24.11±5.12 and 24.68±3.53; p=0.947); Hb concentration (8.46±2.01 vs. 8.33±1.57 and 8.24±0.92; p=0.927); MCV (87.60±7.46 vs. 91.03±9.21 and 83.69±9.22, p=0.055); MCH (31.28±7.77 vs. 30.27±4.27 and 27.61±4.51; p=0.185); MCHC (33.05±7.54 vs. 33.07±3.39 and 32.48±3.13; p=0.928) and RDW-CV (19.61±9.65 vs. 19.96±5.61 and 18.10±4.23; p=0.700) respectively. Conclusions: Of all the studied red cell parameters, only MCV significantly differ between the steady and bone pain crises states of SCA. A drop in MCV was recorded during the bone pain crises; probably reflecting depletion of the large reticulocytes and neocytes during the accentuated red cell sickling and vaso-occlusive events characteristic of this clinical state.