Objective. To evaluate the maternal inflammatory response to microbial invasion of the amniotic cavity (MIAC) in women with preterm labor and preterm prelabor rupture of membranes using selected proteins in the maternal serum. Design. A prospective cohort study. Setting. Labor ward from Salgrenska University Hospital. The evaluation of the maternal inflammatory response in the presence of MIAC in preterm labor and preterm prelabor rupture of membranes. Population. One hundred and sixteen women with preterm labor and 73 women with preterm prelabor rupture of membranes between the gestational ages of 22+0 and 33+6 weeks. Methods. Twenty-seven maternal serum proteins were assayed by a multiple immunoassay. Main outcome measures. The maternal serum inflammatory response was evaluated according to the presence of MIAC. Data were stratified by gestational age. Results. There were few differences in the maternal serum protein levels when MIAC was present in both preterm labor and preterm prelabor rupture of membranes. In preterm prelabor rupture of membranes, higher levels of interleukin-18 (median 654 vs. 361 pg/mL, p= 0.003) and lower levels of interleukin-1β (9.5 vs. 19.9 pg/mL, p= 0.008) and monocyte chemotactic protein-1 (139.1 vs. 212.6 pg/mL, p= 0.039) were observed in women with MIAC. Interleukin-6 (20.8 vs. 13.9 pg/mL, p= 0.019) was the only biomarker that increased significantly in preterm labor complicated with MIAC. All of the differences between preterm labor and preterm prelabor rupture of membranes were observed at less than 32+0 weeks of gestation. Conclusions. A weak maternal inflammatory response in the serum was observed in women with MIAC.