Background: The epidemic of COVID-19 has rapidly spread worldwide, with millions of confirmed cases and related deaths. Numerous efforts are being made to clarify how the infection progresses and potential factors associated with disease severity and mortality. We investigated the mortality in Greek hospitalized COVID-19 patients and also the predictors of this mortality. Methods: Study population included 512 COVID-19 patients admitted to the hospitals of the Attica region of Greece. Patients demographic characteristics, comorbidities, allergies, previous vaccination for seasonal influenza virus, admission to ICU, intubation, and death were recorded. Potential predictors of in-hospital mortality were identified by regression analysis. Results: The mean age of hospitalized patients was 60.4 years, and was higher in patients who deceased. The most common comorbidities were respiratory diseases, hypertension, gastrointestinal disorders, dyslipidemia, mental health diseases, asthma, diabetes mellitus and cardiovascular diseases. The need for ICU care and intubation was significantly higher among patients who died. The mortality rate was 15.8% (81 out of 512). Age ≥65 years, cancer, chronic kidney disease, endocrine diseases, central nervous system disorders, anemia, and intubation were independently associated with increased in-hospital mortality, while allergies and previous influenza vaccination were associated with decreased in-hospital mortality. Conclusion: Our finding of a beneficial effect of allergies and influenza vaccination against COVID-19 infection merits further investigation, as it may shed light in the mechanisms underlying disease progression and severity. Most importantly, it may assist in the implementation of efficient protective measures and public healthcare policies.