Mass media is known to set agenda for public discussion, most especially when it has to do with people’s lives and health issues. Monkey pox is an emerging viral zoonotic disease which is caused by monkey pox virus. The study looked at mass media health comprehension and behavioural responses of Nigerians to the prevention of monkey pox disease. The study was anchored on the agenda setting theory while the simple random probability sampling technique was adopted with a sample size of 400 respondents from Ibadan North Local Government. The study found out that majority of the respondents do not understand or know what monkey pox disease is and how it is contacted. In addition, it was found out that the mass media did not attach much importance to its reportage and even when it is reported, majority of the respondents do not understand which actually led to their non-challan behaviour and therefore recommends that the messages on monkey pox disease should be translated to as many languages as possible so that the people will understand how to prevent the monkey pox disease. In addition, the implications of the messages should also be discussed.