Background Globally, xenophobia towards out-groups is frequently increased in times of economic and political instability, such as in infectious disease outbreaks. This systematic review aims to: (1) assess the xenophobic attitudes and behaviors towards migrants during disease outbreaks; and (2) identify adverse health outcomes linked to xenophobia. Methods We searched nine scientific databases to identify studies measuring xenophobic tendencies towards international migrants during disease outbreaks and evaluated the resulting adverse health effects. Results Eighteen articles were included in the review. The findings were grouped into: (1) xenophobia-related outcomes, including social exclusion, out-group avoidance, support for exclusionary health policies, othering, and germ aversion; and (2) mental health problems, such as anxiety and fear. Depending on the disease outbreak, different migrant populations were negatively affected, particularly Asians, Africans, and Latino people. Factors such as perceived vulnerability to disease, disgust sensitivity, medical mistrust individualism, collectivism, disease salience, social representation of disease and beliefs in different origins of disease were associated with xenophobia. Conclusions Overall, migrants can be a vulnerable population frequently blamed for spreading disease, promoting irrational fear, worry and stigma in various forms, thus leading to health inequities worldwide. It is urgent that societies adopt effective support strategies to combat xenophobia and structural forms of discrimination against migrants.