People with pre-existing health conditions (PEHC) are vulnerable to viral infection while health literacy (HL) and preventive behaviors (PB) have been shown to benefit people during the COVID-19 pandemic. The aim of this study was to examine the association between PEHC and suspected COVID-19 symptoms (S-COVID-19-S), and to investigate the modification effect of HL and PB. A cross-sectional study was conducted on 8291 participants visiting outpatient departments at 18 hospitals and health centers across Vietnam from 14 February to 31 May 2020. Data were collected regarding participant’s characteristics, HL, PB, PEHC, and S-COVID-19-S. Regression models were used for analyzing the associations. Results showed that people with PEHC had a 3.38 times higher likelihood of having S-COVID-19-S (odds ratio, OR, 3.38; 95% confidence interval, 95% CI, 3.01, 3.79; p < 0.001). In comparison to participants without PEHC and with the lowest HL score, those with PEHC and one HL score increment had a 7% lower likelihood of having S-COVID-19-S (OR, 0.93; 95% CI, 0.92, 0.94; p < 0.001). In comparison to participants without PEHC and not adhering to mask wearing, those with PEHC and adhering to mask wearing had a 77% lower likelihood of having S-COVID-19-S (OR, 0.23; 95% CI, 0.16, 0.32; p < 0.001). Higher HL and adherence to mask wearing can protect people from having S-COVID-19-S, especially in those with PEHC.