Background: Sarcopenia and frailty are strongly associated with disease incidence and mortality. However, there is limited evidence regarding their joint association with health outcomes. This study aimed to investigate the joint association of sarcopenia and frailty with cardiovascular disease (CVD), respiratory disease and cancer incidence and mortality as well as all-cause mortality in middle-aged and older adults in the UK Biobank study. Methods: 316,980 UK Biobank participants were included in this prospective study (53.1% women). Sarcopenia was defined according to the EWGSOP2 2019. Frailty was defined using a modified version of the Fried criteria. Combined classifications of sarcopenia and frailty were generated with the following seven subgroups derived: i) normal, ii) non-sarcopenic/pre-frail, iii) non-sarcopenic/frail, iv) pre-sarcopenic/pre-frail, v) pre-sarcopenic/frail, vi) sarcopenic/pre-frail, and vii) sarcopenic/frail. No participants had (pre)sarcopenia but not frailty. Associations between these exposures and health outcomes (incidence and mortality from cardiovascular and respiratory diseases, cancer, as well as, all-cause mortality) were investigated using Cox-proportional hazard models. Results: 51.7% of the participants were not sarcopenic nor frail (normal), 41.3% were pre-frail or frail, 6.5% pre-sarcopenia and frail (including pre-frail) and 0.5% as having both sarcopenia and frailty (including pre-frailty). The combination sarcopenic/frail showed the strongest association with CVD (HR: 1.68 [95% CI: 1.22 to 2.30]) and respiratory disease incidence (HR: 1.77 [95% CI: 1.40 to 2.24]) and for mortality from all-cause (HR: 2.27 [95% CI: 1.64 to 3.13]), respiratory disease (HR: 3.50 [95% CI: 1.97 to 6.23]), and cancer (HR: 1.92 [95% CI: 1.08 to 3.38]). Finally, when we investigated the associations between the outcomes and exposures by age groups (≥and <60 years), we identified that, for many outcomes and categories, the associations were higher in younger individuals compared with older adults. Conclusion: Our findings indicate that different combinations of sarcopenia and frailty were associated with adverse health outcomes, highlighting the joint association between both conditions. However, those individuals with sarcopenia and frailty showed the strongest associations with CVD and respiratory disease incidence and mortality for all-cause and respiratory disease and cancer.