Sickle cell disease is a hereditary disease caused by a hemoglobin variant, known as hemoglobin S. This hemoglobin variant has a high frequency in areas where malaria is prevalent, because heterozygous genotype has a protective action against malaria infection. We evaluated evidence of over-dominance or deviation from Hardy- Weinberg equilibrium for the HbS gene in Buenaventura, an afro-descendent population with actual medium endemicity of malaria, located in the Colombian Pacific Coast. 820 healthy individuals were analyzed (from eight months to 80 years old) from Buenaventura, Colombia, and the β -globin locus was genotyped by PCR-RFLP. It was analyzed to establish deviation from Hardy – Weinberg and selection coefficient. Hemoglobin S frequency was 3.1% and the population was found in Hardy- Weinberg equilibrium. However, the selection coefficient for allele S decreased its value of 1 (under 12 years old) to 0.625 (13 to 17 years old), similar to the selection coefficient of allele A (s1=0.61). Although the total population found in H-W equilibrium, there was a decrease in the coefficient of selection on hemoglobin S in the range of 13 to 17 years old, which is within the age range of the greatest malaria infection in this population. This may be an indication of a selection to the S over-dominance hemoglobin possibly, at least in this age group of the population.   Keys words: Hemoglobin S, Buenaventura, malaria resistant, over-dominance, fitness, selection coefficient.