We sought to examine how the near-lockdown measures, announced by the Israeli government in an effort to contain the COVID-19 outbreak, impacted the self-rated health (SRH), health behaviors, and loneliness of people with chronic illnesses. An online cross-sectional survey was carried out about one month (20–22 April 2020) after the Israeli government reinforced the severe social distancing regulations, among a convenience sample of 315 participants (60% women) with chronic conditions (27% metabolic, 17% cardiovascular, 21% cancer/autoimmune, 18% orthopedic/pain, 12% mental-health). Results suggested that about half of the participants reported a decline in physical or mental SRH, and as many as two-thirds reported feeling lonely. A significant deterioration in health behaviors was reported, including a decrease in vegetable consumption (p = 0.008) and physical activity (p < 0.001), an increase in time spent on social media (p < 0.001), and a perception among about half of the participants that they were eating more than before. Ordinal regression suggested that a decline in general SRH was linked with female gender (p = 0.016), lack of higher education (p = 0.015), crowded housing conditions (p = 0.001), longer illness duration (p = 0.010), and loneliness (p = 0.008). Findings highlight the important role of loneliness in SRH during the COVID-19 lockdown period. Future studies are warranted to clarify the long-term effects of social-distancing and loneliness on people with chronic illnesses.