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The Canarypox virus (CNPV) infects captive and wild canaries and cause high mortality and substantial economic losses especially in Middle East countries. Currently, unapproved and illegally imports of embryo propagated, freeze-dried, and live CNPV vaccines are being used by individuals for personal uses in Iran and the region against canarypox disease. The aim of this work was to prepare the stage for the design of a peptide vaccine against canarypox disease. Two immunogenic CNPV proteins were chosen based on homology to antigens from Poxine®, HP1-440 and FP9 strains in fowlpox virus. MHC II specific epitopes of candidate proteins were characterized using various bioinformatics tools. The predicted epitopes were modeled and docked to HLA-DRB1 0101, 0301, 0401, 0405 and 1501 receptors. The stability of docked complexes was evaluated through molecular dynamic simulations. Also, an experimental epitope in vaccinia virus for MHC I receptors was chosen and its canary homolog was docked to two BF receptors in chicken. Due to the critical role of MHC class II in confronting with poxvirus, the IFNAIILWITYAL, LRQLYDVIIPPR, YYNRITSIHM and YRHDDIIAT epitopes were selected among 13 predicted epitopes for MHC class II receptors after docking and MD evaluations. Moreover, due to its long-lasting CD8+ T cell memory responses, the homolog of an experimental epitope from Vaccinia virus (VP35#1) in Canary was evaluated and proposed as potential epitope SLSAYIVSK. These candidate epitopes of high binding affinities may be considered to be included as most effective epitopes for designing epitope-based vaccines against CNPV infection. [ABSTRACT FROM AUTHOR]