© 2016 Wiley Periodicals, Inc. Connective tissue (CT) proteins in jumbo squid (Dosidicus gigas) play an important role because they are the responsible for the union between various cells; hence, there is a close relationship between their functions and muscle firmness during ice storage. In this study, the thermal resistance and solubility of the CT extracted from the fins, mantle and arms of jumbo squid during ice storage (20 days) was evaluated. The CT was fractionated based on solubility [NaCl-soluble (SSCT) and insoluble (ICT)]. The solubility of the CT was affected during ice storage. An increase in the thermal resistance of the SSCT after 10 days with a subsequent decrease was found in the mantle. Furthermore, the ICT was thermally more resistant than the SSCT in all the anatomical regions. Finally, the electrophoretic profile revealed that structural changes occurred, causing changes in its solubility, due to an increase in the thermal resistance. Practical Applications: Jumbo squid (Dosidicus gigas) is an important seafood resource in Mexico, which is commercialized primarily iced and fresh-frozen. Its muscle connective tissue (CT) has different physicochemical characteristics that differ from other seafood products; it is thermally more resistant and might be responsible for the textural changes during ice storage. Moreover, specific studies about the behavior of CT proteins in such organism may result in improved post-catch management of jumbo squid muscle, focused on the processing of the species in the food industry or anywhere that CT proteins are used as raw material. The main objective of this research is to investigate solubility changes and thermal resistance of CT proteins of iced jumbo squid mantle.