Background: We characterized bacterial isolates from the nasopharynx of 84 Sickle cell disease patients 78 of whom were HbSS and 6 HbSC aged 4 four months to 15 years at Wesley Guild Hospital, Ilesa, southwestern Nigeria between February-September, 2014. Method: Sterile cotton-tipped initially dipped into sterile saline thereafter was introduced into nasopharynx of each patient and thereafter applied onto sterile thioglycolate medium and incubated at 370 C for 24 hr, When growth was noticed, samples were inoculated onto enriched, selective and differential bacteriologic media. Bacterial colonies that grew on such media were picked and characterized by Grams' reaction, cultural, morphologic and biochemical methods. Antibiotic sensitivity tests were determined by the disc diffusion method. Demographic data relating to severity of SCD were provided. Results: Altogether, 119 isolates were cultured from the nasopharynx. Gram positive bacteria predominated (65.54%) and Corynebacterium spp (44.53%) dominated comprising of 19 (35.84%) Corynebacterium xerosis 11 (20.75%) Corynebacterium diphtheriae, 10 (18.86) Corynebacterium pseudodiphtheriticum, 8 (15.09%) Corynebacterium ulcerans, 3 (6.66%) Corynebacterium spp and 2 (3.77%) Corynebacterium jeikeium. Other Gram positive rods cultured were Arcanobacterium haemolyticum 6 (5%). Bacillus subtilis was 3 (2.5%), Actinomyces isrealli 3 (2.5%) and Norcadia asteroids 1 (0.84%). Low frequency of nasopharyngeal colonization recorded for Haemophilus influenzae 4.2%, S. pneumoniae 2.5% and S. aureus 4 (3.36%) and multiresistance was widespread for most isolates.