BACKGROUND: The COVID-19 pandemic influenced many to consider methods to reduce human contact and ease the burden placed on health care workers. Conversational agents or chatbots are a set of technologies that may aid with these challenges. They may provide useful interactions for users, potentially reducing the health care worker burden while increasing user satisfaction. Research aims to understand these potential impacts of chatbots and conversational recommender systems and their associated design features. OBJECTIVE: The objective of this study was to evaluate user perceptions of the helpfulness of an artificial intelligence chatbot that was offered free to the public in response to COVID-19. The chatbot engaged patients and provided educational information and the opportunity to report symptoms, understand personal risks, and receive referrals for care. METHODS: A cross-sectional study design was used to analyze 82,222 chats collected from patients in South Carolina seeking services from the Prisma Health system. Chi-square tests and multinomial logistic regression analyses were conducted to assess the relationship between reported risk factors and perceived chat helpfulness using chats started between April 24, 2020, and April 21, 2022. RESULTS: A total of 82,222 chat series were started with at least one question or response on record; 53,805 symptom checker questions with at least one COVID-19-related activity series were completed, with 5191 individuals clicking further to receive a virtual video visit and 2215 clicking further to make an appointment with a local physician. Patients who were aged >65 years (P<.001), reported comorbidities (P<.001), had been in contact with a person with COVID-19 in the last 14 days (P<.001), and responded to symptom checker questions that placed them at a higher risk of COVID-19 (P<.001) were 1.8 times more likely to report the chat as helpful than those who reported lower risk factors. Users who engaged with the chatbot to conduct a series of activities were more likely to find the chat helpful (P<.001), including seeking COVID-19 information (3.97-4.07 times), in-person appointments (2.46-1.99 times), telehealth appointments with a nearby provider (2.48-1.9 times), or vaccination (2.9-3.85 times) compared with those who did not perform any of these activities. CONCLUSIONS: Chatbots that are designed to target high-risk user groups and provide relevant actionable items may be perceived as a helpful approach to early contact with the health system for assessing communicable disease symptoms and follow-up care options at home before virtual or in-person contact with health care providers. The results identified and validated significant design factors for conversational recommender systems, including triangulating a high-risk target user population and providing relevant actionable items for users to choose from as part of user engagement.