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Background Blended learning forms the natural evolution of learning in the contemporary time to cope with current challenges to meet the educational needs of students. Objectives To determine the factors that affect students' use of blended learning during coronavirus disease 2019 at Assiut University. Study design Descriptive cross-sectional. Settings Ten colleges that were selected by simple random sampling from each sector (medical and nonmedical). Participants One thousand six hundred forty university students. Patients and methods One tool divided into two parts: part I: student personal data; part II: scale to examine the factors influencing blended learning use. Results Lecturer's factor had the high moderate mean±SD 3.11±0.95, followed by technical support 3.00±0.99, while usability and information quality with low medium mean ±SD (2.87±0.99 and 2.87±0.96, respectively). Also, there was statistically significance differences between factors influencing blended learning use and college type, age of students, and class with P value of 0.000. Conclusion Factors of lecturers, technical support, and information quality had valuable effect on the university students' use of blended learning. Recommendation The university staff should encourage their students to use blended learning as a preferable approach for enhancing their interaction and communication skills. [ABSTRACT FROM AUTHOR]