The COVID-19 pandemic has substantial implications for physical and mental wellbeing. This study investigated changes, over time, in lifestyle behaviors and perceived stress during the initial phase of the pandemic and associations with COVID-19 symptoms, in the Dutch general population. An online longitudinal survey study was performed with pre-lockdown measurements in February, and subsequently in April and June 2020 (n = 259, mean age 59 ± 14 years, 59% women). Self-report questionnaires were used to assess weight, diet quality, physical activity, alcohol intake, and smoking. Perceived stress was measured using the validated perceived stress scale (PSS-10). The presence of COVID-19 symptoms (yes/no) was defined as fever, or >3 of the following symptoms: weakness/tiredness, muscle ache, dry cough, loss of smell/taste, and breathing difficulties. Data were analyzed using linear mixed models, adjusted for age, sex, educational level, marital status and (change in) employment status. Minimal increases over time were observed in alcohol intake (0.6 ± 0.7 to 0.7 ± 1.1 glasses/day, p = 0.001) and smoking (9.5 ± 8.7 to 10.9 ± 9.4 cigarettes/day among 10% smokers, p = 0.03), but other lifestyle behaviors remained stable. In April 2020, 15% reported COVID-19-related symptoms, and in June 2020, this was 10%. The presence of COVID-19 symptoms was associated with increased perceived stress (p interaction = 0.003) and increased alcohol consumption (p interaction = 0.03) over time. In conclusion, in this prospective study, COVID-19 symptoms were associated with increases in perceived stress and alcohol consumption. Future research on biopsychosocial determinants and underlying mechanisms of lifestyle changes, as a response to the COVID-19 pandemic, is needed.