Purpose: To investigate if blood biomarkers could indicate early signs of lung damage or cardiovascular risk due to exposure to grain dust. Materials and methods: Pneumoproteins and markers of inflammation and platelet activation were analysed in blood samples of 102 grain elevator and compound feed mill workers. Differences between exposed (n = 67) and controls (n = 35), and associations with exposure measurements and respiratory health were investigated by multiple linear regression analyses. Results: Concentrations of CC-16 and IL-6 were higher in exposed workers compared with controls (p < 0.001 for both), whereas fibrinogen was lower (p = 0.005). Concentrations of CRP, TNF-α, sCD40L and sP-selectin were similar in both groups. Serum CC-16 was significantly higher in workers with farm childhood, regardless of exposure. The impact of farm childhood on CC-16 interacted with smoking. None of the biomarkers were associated with exposure measurements or any of the tested respiratory health parameters. Conclusion: Dust exposure induced inflammatory and anti-inflammatory reactions, but did not induce systemic inflammation and had no effect on platelet activation. No cause–effect relationship could be established in spite of relatively high exposure levels, particularly to endotoxin. Whether increased serum CC-16 is an early sign of lung damage or a reversible defense reaction remains unclear.