Hemoglobinopathies can disturb a patient’s life style leading to community problems. Premarital screening is an important tool to control and minimize hemoglobinopathies. This study aimed to assess and improve the awareness and attitude of King Khalid University (KKU) [Abha, Kingdom of Saudi Arabia (KSA)] students in the Aseer Region, regarding hemoglobinopathies and the National Premarital Screening Programme (NPMS) in addition to screening for hemoglobin (Hb) variants of students who agreed to participate. This study was an interventional educational prospective study of electronic-lectures (e-lectures) that addressed some important issues of hemoglobinopathies and premarital screening. Six hundred and eleven students were interviewed during the academic year 2017/2018, using closed-ended questionnaires that distributed before and after intervention. Blood samples were taken from 114 students who agreed to check their Hb type by the D-10 Hemoglobin Testing System. The results revealed significant changes in knowledge and attitude of students toward hemoglobinopathies and premarital counseling after intervention. These results reflected the need for easily accessible and continuous health education programs for students to increase their awareness and attitude toward hemoglobinopathies. Laboratory results for 114 students revealed seven cases with microcytic hypochromic anemia (6.1%); they were all females. Blood screening for Hb variants revealed another two females (1.75%) with sickle cell trait (Hb AS). Electronic-health (E-health) is an efficient tool for improving the awareness and attitude of the community toward hemoglobinopathies. Screening blood tests for detection of hemoglobinopathies should be provided to young adults at an earlier stage (before marriage) to decrease the incidence of hereditary diseases in the community.