Background Patients with critical illness can lose more than 15% of muscle mass in one week, and this can have long-term detrimental effects. However, there is currently no synthesis of the data of intensive care unit (ICU) muscle wasting studies, so the true mean rate of muscle loss across all studies is unknown. The aim of this project was therefore to systematically synthetise data on the rate of muscle loss and to identify the methods used to measure muscle size and to synthetise data on the prevalence of ICU-acquired weakness in critically ill patients. Methods We conducted a systematic literature search of MEDLINE, PubMed, AMED, BNI, CINAHL, and EMCARE until January 2022 (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD420222989540. We included studies with at least 20 adult critically ill patients where the investigators measured a muscle mass-related variable at two time points during the ICU stay. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and assessed the study quality using the Newcastle–Ottawa Scale. Results Fifty-two studies that included 3251 patients fulfilled the selection criteria. These studies investigated the rate of muscle wasting in 1773 (55%) patients and assessed ICU-acquired muscle weakness in 1478 (45%) patients. The methods used to assess muscle mass were ultrasound in 85% (n = 28/33) of the studies and computed tomography in the rest 15% (n = 5/33). During the first week of critical illness, patients lost every day −1.75% (95% CI −2.05, −1.45) of their rectus femoris thickness or −2.10% (95% CI −3.17, −1.02) of rectus femoris cross-sectional area. The overall prevalence of ICU-acquired weakness was 48% (95% CI 39%, 56%). Conclusion On average, critically ill patients lose nearly 2% of skeletal muscle per day during the first week of ICU admission.