Sickle cell anemia (SCA) is a common inherited kind of hemolytic anemia in Africa and some areas of Asia. In Saudi Arabia, SCA is prevalent as well. The patient of SCA is prone to some bacteria species more than the others, and Salmonella is one of the most prevalent infections in SCA that were known to cause bacteremia, osteomyelitis, septic arthritis, and gastroenteritis. Herein, we report a 7-years old girl who presented with a history of fever for five days and jaundice with abdominal pain and mild respiratory distress. Later, the patient was diagnosed to have infective endocarditis due to Salmonella enterica subspecies salamae (subgroup II). The patient improved completely after receiving proper antibiotics. To the best of our knowledge, there is only one case of adult SCA that has been reported with infective endocarditis due to Salmonella entrica but no reported case in pediatric.