Each season, crops face simultaneous or successive multiple infections. Yet cultivar resistance is often bred against one pest at a time, and screened under single infections. This raises the question of resistance expression bred under mono‐infections when exposed to multiple infections. We tackled this question by measuring the level of quantitative resistance of potato cultivars to either Globodera pallida or Phytophthora infestans under single or multiple infections, using potato virus Y (PVY) or Rhizoctonia solani as the co‐infector. Overall, co‐infection resulted in less multiplication of the target pathogen compared to single infection, although this reduction did not always reach statistical significance. A preliminary assessment of defence gene expression in plants infected with P. infestans alone or together with PVY or R. solani suggested that P. infestans repressed defence genes previously triggered by PVY, but boosted the expression of these genes when primed by R. solani. Together, these data support the view that resistance expression is impacted by co‐infection, and that it should be screened under multiple infection situations to be best assessed and exploited as a component of Integrated Pest Management strategies.