INTRODUCTION: COVID-19 is a viral respiratory disease, which became a global threat to public health. Specific subsets of the population are more vulnerable, namely those with chronic diseases. We aimed to estimate the share of the Portuguese population at the highest risk for complications following COVID-19 infection due to both old age and specific comorbidities. MATERIAL AND METHODS: Our sample included all people aged 65 years and above (2215 men and 3486 women) who participated in the fifth Portuguese National Health Interview Survey, conducted in 2014. In order to project the potential population at highest risk for COVID-19, we used the latest available official demographic estimates from the National Institute of Statistics - INE 2018. We used a more restrictive definition of risk combining old age criteria and the following chronic conditions as potential risk factors for COVID-19 according to the available literature: hypertension, diabetes, chronic obstructive pulmonary disease, cardio- and cerebrovascular disease. RESULTS: We estimated that 15.5% (n = 1 560 667) of the Portuguese population might be at increased risk for complications from COVID-19 because of old age and existing chronic conditions. Such estimates vary across the country (from 1.7% in Azores to 33.7% in Northern Portugal). Northern Portugal not only has the highest prevalence of selected morbidity (72.8%) within mainland Portugal, but also has the largest population at risk for COVID-19 (n = 526 607). This was followed by the Lisbon and Tagus Valley region (n = 408 564) and Central Portugal (n = 388 867). DISCUSSION: Our results should encourage authorities to continue protecting those more vulnerable to the pandemic threat, particularly on those areas of the country which are more likely to be further affected. CONCLUSION: We projected a considerable number of Portuguese people at the highest risk for severe COVID-19 disease due to both old age and pre-existing chronic conditions. Such estimates vary across the country.