Abstract The response of serum amyloid A (SAA) concentrations in serum and saliva during a natural porcine respiratory and reproductive syndrome (PRRS) outbreak was investigated. Basal levels of SAA were reliably determined and significant differences in SAA were found between diseased and healthy pigs in both sample types (serum SAA medians 78.3 vs. 55.74mg/L, respectively; salivary SAA medians 8.97 vs. 2.52mg/L, respectively; P<0.001). In serum, an SAA cut-off value of 66.4mg/L showed 68.9% sensitivity and 68.09% specificity, while in saliva an SAA cut-off value of 5.59mg/mL showed a sensitivity–specificity pair of 69–66%. Furthermore, it was observed that the growth stage of animals should be accounted to correctly interpret SAA measurements, since more accurate cut-off values could be determined and a particular behaviour of salivary SAA was identified in post-weaning pigs. Salivary and serum SAA measurements can therefore be confirmed as a valuable tool to consistently discriminate between healthy and PRRS-affected pigs.