The uncertainty surrounding the effect of infectious diseases on nursing students' attitudes toward the nursing profession worldwide exists. This study sought to examine the association between fear of infectious diseases and students' attitudes toward the nursing profession. METHODS This quantitative descriptive cross-sectional study used a convenience sample of 477 students enrolled in nursing programs from three universities located in urban and non-urban areas in Saudi Arabia. RESULTS The study revealed a positive attitude toward nursing and minimal fear of infectious diseases. Junior nursing students reported significantly better attitudes and preferences toward the nursing profession than senior nursing students. Students who reported positive attitudes toward the nursing profession significantly had no intension to discontinue or transfer from nursing programs, whereas students with low attitudes reported significant intention to discontinue their enrollment in the nursing programs. Students in urban universities reported higher significant fear of infectious diseases compare to non-urban. The study revealed a significant negative correlation between fear of infectious diseases and students' preference for the nursing profession. CONCLUSIONS Nurse educators need to support senior nursing students' attitudes toward the nursing profession and reduce their fear of infectious diseases, particularly among students studying in urban areas.