Background/Objectives: Myokines can modulate organ function and metabolism, offering a protective profile against ICU complications beyond preventing local muscle wasting. This scoping review aims to explore and summarize the evidence regarding the secretion of myokines and their potential local or systemic effects in critically ill patients. Methods: A scoping review following Joana Briggs Institute recommendations was conducted. A systematic search of MEDLINE (Ovid), Embase (Ovid), CENTRAL, CINAHL (EBSCOhost), WoS, and Scopus was conducted from inception to February 2023. We included primary studies evaluating myokine secretion/concentration in critically ill adults undergoing physical rehabilitation interventions. Two independent reviewers performed study selection and data extraction. Results: Seventeen studies published between 2012 and 2023 were included. Most were randomized clinical trials (47%). Physical rehabilitation interventions included electrical muscle stimulation, as well as passive and active mobilization, delivered alone or combined, in single or daily sessions lasting 20–60 min. Twelve studies (70%) evaluated interleukin-6, while interleukin-10, tumour necrosis factor-α, Interleukin-8, and myostatin were also commonly studied. Thirteen studies (76%) reported changes in myokine secretion or gene expression, although no clear concentration change pattern emerged. Myokines involved in muscle protein synthesis and breakdown may protect against muscle waste and weakness. Conclusions: The study of myokine dynamics in critically ill patients highlights the systemic impact of physical rehabilitation. This emerging field has grown in interest over the past decade, offering significant research potential. However, challenges such as study design, small sample sizes, and variability in physical therapy protocols hinder a comprehensive understanding of myokine responses.