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Background: Low-grade inflammation in early childhood might protect from allergic diseases later in life. Our aim was to examine the effects of different environmental factors on low-grade inflammation measured with serum high-sensitivity C-reactive protein (hsCRP) at the age of 4.5 years., Methods: The high-sensitivity CRP values (n = 653) and serum-specific IgE concentrations were measured from 4.5-year-old children in rural areas in five European countries (Austria, Finland, France, Germany, and Switzerland). Children belonged to the prospective multi-center PASTURE birth cohort. Data on early and current farming environment and domestic animal exposure were collected by questionnaires., Results: Females as well as obese or very obese children at age of 4.5 years had higher hsCRP values than males (aOR 1.84 95% CI 1.27-2.66) and healthy weight children (aOR 4.47 95% CI 1.94-10.31), respectively. Levels were lowest in the summer. Few associations were detected between hsCRP values and farm environmental factors or atopic sensitization. However, there was evidence of children with low levels of hsCRP (below the detection limit) who had increased prevalence of sensitization to inhaled and seasonal allergens. Among non-sensitized children, spending time in stables was associated with reduced hsCRP (15 min-10 h aOR 0.40 95% CI 0.16-0.96 and ≥10 h aOR 0.25 95% CI 0.07-0.90), and among sensitized children, maternal smoking was associated with higher hsCRP values (aOR 2.51 95% CI 1.12-5.59)., Conclusion: We found few associations between early environmental farming factors and hsCRP levels, and between hsCRP levels and atopic sensitization in 4.5-year-old children. However, our results suggest that the role played by the environmental factors in low-grade inflammation may differ between sensitized and non-sensitized children., (© 2012 John Wiley & Sons A/S.)