Studies suggest that heat shock proteins (Hsps), Hsp70 in particular, may play a role in embryogenesis and reproduction. As the first trimester is the critical period of human fetal development, we tested whether there is an association between Hsp70 expression in lymphocytes and adverse pregnancy outcomes (APOs) during that period. We measured lymphocyte Hsp70 levels by immunoblot in 55 pregnant women with APOs and 110 well-matched controls selected from 778 pregnant women in a nested case-control study. Multivariate logistic regression models were used to investigate the association between lymphocyte Hsp70 levels and risk of developing APOs. Our data showed that Hsp70 levels in women with APOs, especially those younger than 29 years old, were significantly higher than controls (193 vs 135 units, P < 0.001) and that the elevated Hsp70 levels were associated with a significantly increased risk of APOs (adjusted OR = 1.014; 95% CI = 1.008–1.020, P < 0.001). Our results also showed that the sensitivity, specificity, and positive and negative predictive values were 78%, 60%, 50%, and 85%, respectively, among these pregnant women. Adjusted ORs and 95% CI for the association between a Hsp70 value > 153 IOD and APOs were statistically significant (OR = 8.78, 95% CI = 2.79–27.64, P < 0.001). These results suggest that Hsp70 may play a role in the etiology of APOs. However, the underlying mechanisms for the elevation of Hsp70 in women with APOs and whether Hsp70 can be applied as a clinical indicator of APOs warrant further investigations.