AIM Cachexia is characterized by losses in lean body mass and its progression results in worsened quality of life and exacerbated outcomes in cancer patients. However, the role and impact of fibrosis during the early stages and development of cachexia in under-investigated. The purpose of this study was to determine if fibrosis occurs during cachexia development, and to evaluate this in both sexes. Methods Female and male C57BL6/J mice were injected with PBS or Lewis Lung Carcinoma (LLC) at 8‐week of age and tumors were allowed to develop for 1, 2, 3, or 4 weeks. 3wk and 4wk female tumor‐bearing mice displayed a dichotomy in tumor growth and were reassigned to high tumor (HT) and low tumor (LT) groups. In vitro analyses were also performed on co-cultured C2C12 and 3T3 exposed to LLC conditioned media. Immunohistochemistry and quantitative PCR analysis were used to investigate fibrosis and fibrosis related signaling in skeletal muscle. Results Collagen deposition in skeletal muscle was increased in the 1wk, LT and HT groups in female mice. However, collagen deposition was only increased in the 4wk group in male mice. In general female mice displayed earlier alterations in ECM related genes beginning at 1 wk post-LLC injection. Whereas this was not seen in males. Conclusions While overall tumor burden is tightly correlated to cachexia development in both sexes, fibrotic development is not. Male mice did not exhibit early-stage alterations in ECM related genes contrary to what was noted in female mice.