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This book constitutes the refereed post-conference proceedings of 9 workshops held at the 35th International ISC High Performance 2021 Conference, in Frankfurt, Germany, in June-July 2021: Second International Workshop on the Application of Machine Learning Techniques to Computational Fluid Dynamics and Solid Mechanics Simulations and Analysis; HPC-IODC: HPC I/O in the Data Center Workshop; Compiler-assisted Correctness Checking and Performance Optimization for HPC; Machine Learning on HPC Systems;4th International Workshop on Interoperability of Supercomputing and Cloud Technologies;2nd International Workshop on Monitoring and Operational Data Analytics;16th Workshop on Virtualization in High-Performance Cloud Computing; Deep Learning on Supercomputers; 5th International Workshop on In Situ Visualization. The 35 papers included in this volume were carefully reviewed and selected. They cover all aspects of research, development, and application of large-scale, high performance experimental and commercial systems. Topics include high-performance computing (HPC), computer architecture and hardware, programming models, system software, performance analysis and modeling, compiler analysis and optimization techniques, software sustainability, scientific applications, deep learning.