Zonulin has previously been related to intestinal permeability in various inflammatory diseases, and more recently to the physiopathology of severe COVID-19 infections. We analysed serum samples from a previous study of a Peruvian cohort of hospitalised COVID-19 patients, for the quantification of zonulin by sandwich ELISA. Comparisons with clinical data, haematological and biochemical parameters and cytokine/chemokine levels were made. We found higher baseline zonulin levels in deceased patients, and zonulin was associated with fatal outcome in multivariable analyses, even after adjustment for age, gender, and obesity. There were also positive correlations between zonulin, creatinine, D-dimer values and prothrombin time, while inverse correlations were found for Sa/FiO2 ratio and CCL5 (RANTES). Further longitudinal studies are recommended to analyse the variation of zonulin levels over time as well as their relationship with long-COVID.