The coronavirus disease 2019 (COVID-19) pandemic has caused a lot of ethical controversy in the equal provision of healthcare, including vaccination. Therefore, our study was designed to assess the impact of Ho Chi Minh City’s policy to hold the second dose of the COVID-19 vaccine. Using a cross-sectional study design to assess low saturation of peripheral oxygen (SPO2) risk based on vaccination status, we included patients who were confirmed to have SARS-CoV-2 and were treated at home. The stepwise method was used to determine participants’ low SPO2 risk-related factors. The average age of the 2836 respondents was 46.43 ± 17.33 (years). Research results have shown that seven factors are related to the low SPO2 status of participants, including age, sneezing, shortness of breath, coughing, and fainting as COVID-19 symptoms, the number of people living with COVID-19, and a history of lung disease. A statistically significant (p = 0.032) finding in this study was that fully vaccinated patients had a 6% lower risk of low SPO2 compared to the first dose less than 21 days group. This result was similar in the vaccine holder group (p < 0.001). Holding the second dose of the COVID-19 vaccine is associated with a lower SPO2 risk than that of fully vaccinated patients. Therefore, this approach should be considered by governments as it could bring a greater benefit to the community.