Abstract Background Frailty, sarcopenia, cachexia and malnutrition are clinical conditions that share similar diagnostic criteria. This study aimed to investigate the clustering and mortality risk among these clinical conditions in middle- and older-aged adults. Methods 111 983 participants from UK Biobank were included. Sarcopenia was defined according to the EWGSOP 2019 while frailty using a modified version of the Fried criteria. Cachexia was defined using the Evans et al. classification and malnutrition using the Global Leadership Initiative on Malnutrition. The exposure variable was categorized as: no conditions; frailty only (one condition); frailty with sarcopenia (two conditions); frailty with ≥2 other conditions (three or four conditions). Its association with all-cause mortality was investigated using Cox-proportional hazard analysis. Results Frailty had the highest prevalence (45%) and was present in 92.1% of people with malnutrition and everyone with sarcopenia or cachexia. Compared with people with no conditions, those with frailty only and frailty with sarcopenia had higher risk of all-cause mortality. Individuals with frailty plus ≥2 other conditions had even higher risk (HR: 4.96 [95% CI: 2.73 to 9.01]). Conclusions The four clinical conditions investigated overlapped considerably, being frailty the most common. The risk of all-cause mortality increased with the increasing number of conditions in addition to frailty.