Background: Throughout history, disease outbreaks have affected humans, and low health literacy (HL) is usually associated with poor health care and prevention, as well as self-efficacy (SE) and reduced Satisfaction with Life (SWL). Purpose: This study investigated the current status and relationship of HL, SE, and SWL of college students in Macao. Methods: A total of 553 valid samples aged 18 to 25 (M=20.4 ±1.16) were collected by stratified and convenient sampling methods in Macao. Three measurement tools included HLS-EU-Q (α = .94), GSES (α = .87), and SWLS (α=.89) were verified validity and reliability. Data were analyzed by SPSS 24.0 with the methods of t-test, one-way ANOVA, and correlation and regression analysis. Result: Overall, the key findings include (1) college students in Macao respectively met a medium level of HL (M=3.6, SD=0.53), SE (M=6.7, SD=1.3), and SWL (M=6.2, SD=1.8). (2) there is a significant difference among various background variables (gender, region, and living environment), (3) there is a positive relationship among HL, SE, and SWL, HL, and SE had a 34.1% explanation on SWL (R²=.341, β=.717, p<0.001). Conclusions: The result is in agreement with other health-related studies. The findings suggested that the higher HL, the higher SWL. Even College students in Macao reached the medium level of HL, SE, and SWL, educational expansion, and community attention are needed. It also assumed that the association between HL and SWL might be mediated by SE.