Background: Avian influenza is considered as a global health problem. Knowledge of the people about avian flu is important to implement different prevention and control measures and to raise the level of their awareness. Objective: was to assess the level of knowledge about avian flu among Primary Health Care Centers (PHCCs) attendees, and to determine possible associations between knowledge and some socio-demographic characteristics. Methods: This was a cross-sectional study conducted in two randomly selected PHCCs in Al-Khobar city, Kingdom of Saudi Arabia (KSA) during 2009. The total sample size was 1420 persons. Data collection was accomplished through using an interviewer-administered questionnaire which was composed of 2 main parts atttendees' socio-demographic characteristics and knowledge questions. The total knowledge score was divided into 2 equal categories: poor and good knowledge. Descriptive statistics, Chi-square test and stepwise logistic regression analysis were used. Results: The majority of the attendees were Saudis (89.4%), of young age (15-<30years) (56.2%) and were married (50.8%). About 41.5% were unemployed, and 42.7% had university or higher education. About three quarters (74.4%) of the PHCCs attendees had good level of knowledge and only 25.6% had poor knowledge regarding avian flu. The stepwise logistic regression analysis showed that the following factors were found to be independently significantly associated with increased level of knowledge: male gender (OR=1.44, CI=1.098-1.890), higher level of education (OR=1.7, 95% CI=1.439-2.009) and younger age (OR=1.546, 95% CI= 1.257-1.902). PHCCs were mentioned by only 2.9% of the attendees as a source of information about avian influenza. Conclusion: Although the majority of PHCCs attendees had good knowledge about avian flu, yet more efforts are needed to give priority to those who had poor knowledge (females, lower educational level, low monthly income and elderly people). Health messages should be designed in a way that they could be understood by all people using all available channels. PHCCs should have more roles in educating the public about avian flu.