Previous theoretical work has suggested that people can accurately perceive disease from others’ appearances and behaviors. However, much of that research has examined diseases with relatively obvious symptoms (e.g., scars, obesity, blemishes, sneezing). Here, we examined whether people similarly detect diseases that do not exhibit such visible physical cues (i.e., sexually transmitted diseases). We found that people could indeed identify individuals infected with sexually transmitted diseases significantly better than chance from photos of their faces. Perceptions of the targets’ affective expression and socioeconomic status mediated participants’ accuracy. Finally, increasing participants’ contamination fears improved their sensitivity to disease cues. These data therefore suggest that people may use subtle and indirect psychological markers to detect some physical diseases from appearance.