Background The COVID-19 pandemic has led to urgent calls for the adoption of telehealth solutions. However, public interest and demand for telehealth during the pandemic remain unknown. Objective We used an infodemiological approach to estimate the worldwide demand for telehealth services during COVID-19, focusing on the 50 most affected countries and comparing the demand for such services with the level of information and communications technology (ICT) infrastructure available. Methods We used Google Trends, the Baidu Index (China), and Yandex Keyword Statistics (Russia) to extract data on worldwide and individual countries’ telehealth-related internet searches from January 1 to July 7, 2020, presented as relative search volumes (RSV; range 0-100). Daily COVID-19 cases and deaths were retrieved from the World Health Organization. Individual countries’ ICT infrastructure profiles were retrieved from the World Economic Forum Report. Results Across the 50 countries, the mean RSV was 18.5 (SD 23.2), and the mean ICT index was 62.1 (SD 15.0). An overall spike in worldwide telehealth-related RSVs was observed from March 11, 2020 (RSV peaked to 76.0), which then tailed off in June-July 2020 (mean RSV for the period was 25.8), but remained higher than pre-March RSVs (mean 7.29). By country, 42 (84%) manifested increased RSVs over the evaluation period, with the highest observed in Canada (RSV=100) and the United States (RSV=96). When evaluating associations between RSV and the ICT index, both the United States and Canada demonstrated high RSVs and ICT scores (≥70.3). In contrast, European countries had relatively lower RSVs (range 3.4-19.5) despite high ICT index scores (mean 70.3). Several Latin American (Brazil, Chile, Colombia) and South Asian (India, Bangladesh, Pakistan) countries demonstrated relatively higher RSVs (range 13.8-73.3) but low ICT index scores (mean 44.6), indicating that the telehealth demand outstrips the current ICT infrastructure. Conclusions There is generally increased interest and demand for telehealth services across the 50 countries most affected by COVID-19, highlighting the need to scale up telehealth capabilities, during and beyond the pandemic.