Patients diagnosed with a chronic disease are at higher risk of influenza complications. This investigation aimed to estimate influenza vaccine uptake rates among healthy subjects and patients with chronic diseases, and to identify barriers to and facilitators of its uptake. This study was a cross-sectional investigation that targeted the general population in the Jazan region of Saudi Arabia. Data were collected via online platforms between October and November 2022. Data were collected via a self-administered questionnaire that assessed the demographics, influenza vaccine uptake, and factors associated with the uptake. A chi-squared test was used to investigate factors associated with the uptake of the influenza vaccine. A total of 825 adult subjects participated in the current investigation. The proportion of male participants was higher (61%) compared to females (38%). The mean age of the participants was 36, with a standard deviation of 10.5. Nearly 30% of the sample reported being diagnosed with a chronic disease. Among the recruited sample, 576 (69.8%) reported having ever received the influenza vaccine, and only 222 participants (27%) indicated that they receive the influenza vaccination annually. Only history of being diagnosed with a chronic disease was statistically associated with the history of ever receiving the influenza vaccine (p< 0.001). Among the 249 participants with a chronic disease, only 103 (41.4%) ever received the influenza vaccine and only 43 (17.3%) of them received the vaccine annually. The main barrier to the uptake was fear of side effects due to the vaccination. A minority of the participants indicated that they were motivated by a healthcare worker to have the vaccine. This suggests an area for further investigation to assess the involvement of healthcare workers in motivating their patients with chronic diseases to have the vaccine.