This book constitutes the refereed proceedings of the 46th International Conference on Current Trends in Theory and Practice of Informatics, SOFSEM 2020, held in Limassol, Cyprus, in January 2020. The 40 full papers presented together with 17 short papers and 3 invited papers were carefully reviewed and selected from 125 submissions. They presented new research results in the theory and practice of computer science in the each sub-area of SOFSEM 2020: foundations of computer science, foundations of data science and engineering, foundations of software engineering, and foundations of algorithmic computational biology.