Salmonella is a major bacterial pathogen in low-income countries, where it circulates among humans, animals, and the environment. Children with sickle cell disease (SCD) are particularly vulnerable to severe Salmonella infections. This study aimed to characterize Salmonella isolates causing infections in Senegalese children with SCD. Using antimicrobial susceptibility testing, whole-genome sequencing, and bioinformatic analysis, we investigated antibiotic resistance, serovar diversity, and virulence factors on 23 isolates from SCD patients with diverse clinical infections. The isolates belonged to 12 serovars, with Enteritidis predominating (n = 7). Twenty-two isolates were fully susceptible to antibiotics, while one was multidrug-resistant. Eight isolates (Enteritidis and Typhimurium) carried a virulence plasmid harboring the spvRABCD gene cluster. Core Salmonella pathogenicity islands (SPIs-1 to -5, -11, and -13), as well as SPI-10 and SPI-23, were detected in all isolates, whereas other SPIs were variably present. These results show high serovar diversity and low antimicrobial resistance among Salmonella isolates in children with SCD in Dakar, Senegal. Our findings suggest that strains causing diarrhea in healthy individuals may also cause invasive disease in SCD patients, highlighting the need for dedicated surveillance in this vulnerable population.