This study evaluated precipitating factors, clinical features, and some laboratory parameters during Vaso-occlusive crisis (VOC) of sickle cell disorder (SCD), with a view to determining the role of malaria infection. Over a period of 16 months, 60 patients with SCD and VOC episodes participated in the study. A questionnaire that was developed and pretested was administered on the patients who were clinically examined. The severity of pains was assessed using visual analogue scale (VAS). 10ml of venous blood was collected for haematological (haematocrit, platelet, leucocyte count); microbiological (malaria parasite density) and immunological (Pf-IgG) tests. Data collected was analyzed using descriptive and inferential statistics; a p-value <0.05 was significant. The results showed that the study population consisted of 52 (87%) HbSS and 8 (13%) HbSC with a mean (+SD) age of 25.3 years (+9.7) and a 95% confidence interval (CI) of 23.0 – 27.7 and overall M: F ratio of 1:1.5. A total of 65 VOC episodes were evaluated with moderate to severe pain occurring in 51%. Malaria parasite was detectatable in 55% of patients, with a mean malaria parasite density of 671 parasite/uL (+ 1087; CI-315.9-1026). Commonly observed symptoms included fever (40%), jaundice (35.4%), headache (23.1%) and vomiting (13.8%). Severe anaemia occurred in 12.2% of patients. Malaria parasitaemia occurred in 61% of patients with fever, 73.9% of patients with jaundice and 75% of patients with severe anaemia. The mean P. falciparum specific IgG (Pf-IgG) absorbance for 44 patients was 2.166 (+0.712, CI 1.956-2.377), the mean Pf-IgG absorbance of HbSC patients was significantly higher than that of HbSS patients (p<0.05). The Pf-IgG in HbSS with splenomegaly significantly correlated with splenic size (P<0.05), but not with parasite density. Eighty percent of patients had used one or more types of analgesics before presentation. The majority of patients (94%) used malaria prophylaxis but with varied adherence and there was no significant difference in the mean malaria parasite density of the different types of prophylaxis. In conclusion, malaria infection occurred in one in two (1:1) episodes of VOC and was associated with fever, jaundice and vomiting to a certain extent. Immunity against P.falciparum malaria correlated with splenic size but not with malaria parasite density in HbSS patients.