Background The uptake of sickle cell trait (SCT) test is challenged by several factors. A community of healthcare professionals educating the public to undergo screening is critical in reducing the disease burden. We investigated knowledge and attitude towards premarital SCT screening among healthcare trainee students who are the next generation of healthcare practitioners. Methods A cross‐sectional design was employed, and quantitative data were collected from 451 female students pursuing healthcare programs at a tertiary institution in Ghana. Descriptive, bivariate, and multivariate logistic regression analysis was performed. Results More than half of the participants were 20–24 years (54.55%) and had good knowledge (71.18%) about sickle cell disease (SCD). Age and school or social media as sources of information were significantly associated with good knowledge about SCD. Students between the age 20–24 (adjusted odds ratio [AOR] = 2.54, confidence interval [CI] = 1.30–4.97) and knowledge (AOR = 2.19, CI = 1.41–3.39) were 3 times and 2 times more likely to have a positive perception about SCD severity. Students who have SCT (AOR = 5.16, CI = 2.46–10.82), whose source of information was family member/friends (AOR = 2.83, CI = 1.44–5.59) and social media (AOR = 4.59, CI = 2.09–10.12) were 5 times, 2 times and 5 times likely to have a positive perception about the susceptibility of SCD. Students whose source of information is school (AOR = 2.06, CI = 1.11–3.81) and who have good knowledge of SCD (AOR = 2.25, CI = 1.44–3.52) were 2 times more likely to have a positive perception about the benefits of testing. Students with SCT (AOR = 2.64, CI = 1.36–5.13) and source of information was social media (AOR = 3.01, CI = 1.36–6.64) were about 3 times more likely to have a positive perception about the barriers to testing. Conclusion Our data shows that high level of SCD knowledge influences positive perceptions about the severity of SCD, the benefits and relatively low barriers to SCT or SCD testing and genetic counseling. Dissemination of SCT, SCD and premarital genetic counseling education should be intensified especially in schools.