Background: Premarital mental screening is an effective primary preventive measure against some genetic disorders and psychological disturbances among youth before marriage. Aim: The study aimed to assess premarital mental screening knowledge and attitude among adults in Aswan City. Methods: A cross-sectional descriptive study was conducted in Aswan City. The study was carried out at Primary Health Care Centers, and University hospital outpatient clinics in Aswan city, a random sample of 399 participants was recruited as the sample size. Data collection utilized three tools: a structured interview questionnaire encompassing studied participant's socio-demographic data, knowledge assessment regarding premarital mental health screening, and attitude assessment toward premarital mental screening.  Results: The majority of study participants (72,4%) had a good knowledge regarding premarital mental screening, and 77.4% of them had a positive attitude toward premarital mental screening compared to 22.6% had a negative attitude. Conclusion: The current study revealed that the majority of study participants had satisfactory knowledge regarding premarital mental screening. They also had a positive attitude towards premarital mental screening. Recommendation: Premarital screening should be added to the existing imposed screening methods with the help of the health sector and mental health screening should be incorporated into both nursing and medical science curriculum.