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<i>Background and Objectives</i>: Early reports on COVID-19 infection suggested that the SARS-CoV-2 virus solely attacks respiratory tract cells. As the pandemic spread, it became clear that the infection is multiorganic. Metabolic associated fatty liver disease (MAFLD) is a chronic liver disease strongly associated with insulin resistance and diabetes. The aim of this study was to assess a possible interplay between MAFLD and COVID-19 infection and its implication in COVID-19 outcome. <i>Materials and Methods</i>: A retrospective observational study, including 130 COVID-19 positive patients was conducted. MAFLD diagnosis was made based on the International Consensus criteria. Patients were divided into two groups, group A (MAFLD) and group B (nonMAFLD). Anthropometric and laboratory analysis were obtained. COVID-19 severity was assessed using the NEWS2 score. Disease outcome was threefold and regarded as discharged, patients who required mechanical ventilation (MV), and deceased patients. <i>Results</i>: MAFLD prevalence was 42%, 67% of patients were discharged, and 19% needed MV. Mortality rate was 14%. MAFLD patients were significantly younger (<i>p</i> < 0.001), and had higher body mass index (<i>p</i> < 0.05), respiratory rate (<i>p</i> < 0.05) and systolic blood pressure (<i>p</i> < 0.05) than nonMAFLD patients. Regarding metabolic syndrome and inflammatory markers: group A had significantly higher glycemia at admission (<i>p</i> = 0.008), lower HDL-c (<i>p</i> < 0.01), higher triglycerides (<i>p</i> < 0.01), CRP (<i>p</i> < 0.001), IL-6 (<i>p</i> < 0.05) and ferritin (<i>p</i> < 0.05) than group B. MAFLD was associated with more prevalent type 2 diabetes (<i>p</i> = 0.035) and hypertension (<i>p</i> < 0.05). MAFLD patients had a more severe disease course (NEWS2 score, 6.5 ± 0.5 vs. 3 ± 1.0, <i>p</i> < 0.05). MAFLD presence was associated with lower patient discharge (<i>p</i> < 0.01) and increased need for MV (<i>p</i> = 0.024). Multiple regression analysis showed that BMI (<i>p</i> = 0.045), IL-6 (<i>p</i> = 0.03), and MAFLD (<i>p</i> < 0.05) are significant independent risk factors for a poor COVID-19 outcome. <i>Conclusions</i>: The prevalence of MAFLD is relatively high. MAFLD patients had a more severe COVID-19 clinical course and worse disease outcome. Our results imply that early patient stratification and risk assessment are mandatory in order to avoid poor outcomes.