Background: Muscle quality index (MQI) is an emerging health indicator obtained by dividing handgrip strength by body mass index (BMI) that needs to be studied in morbidly obese patients (defined by BMI ≥ 35 kg/m2). Objective: To determine the association between MQI, metabolic syndrome (MetS) markers, and cardiorespiratory fitness (CRF), and as a second objective to determine the potential mediation role of MQI in the relationship between abdominal obesity and systolic blood pressure (SBP) in this sample. Methods: This cross-sectional study included 86 severely/morbidly obese patients (age = 41.1 ± 11.9 y, nine men). MQI, metabolic syndrome markers, CRF, and anthropometric parameters were measured. Two groups were developed according to MQI; High-MQI (n= 41) and Low-MQI (n= 45). Results: The Low-MQI group reported higher abdominal obesity (High-MQI: 0.7 ± 0.1 vs. Low-MQI: 0.8 ± 0.1 WC/height;p= 0.011), SBP (High-MQI: 133.0 ± 17.5 vs. Low-MQI: 140.1 ± 15.1 mmHg;p= 0.048), and lower CRF (High-MQI; 26.3 ± 5.9 vs. Low-MQI; 22.4 ± 6.1 mL/kg/min,p= 0.003) than the High-MQI group. Waist-to-height ratio (β: −0.07,p= 0.011), SBP (β: −18.47,p= 0.001), and CRF (β: 5.21,p= 0.011) were linked to MQI. In a mediation model, the indirect effect confirms that MQI is a partial mediator of the association between abdominal obesity with SBP. Conclusions: MQI in morbidly obesity patients reported an inverse association with MetS markers and a positive association with CRF (VO2max). It mediates the relationship between abdominal obesity and SBP.