Purpose: To determine the influence of plaque and progesterone on periodontitis in pregnant women and their relationship with inflammatory mediators. Materials and Methods: A longitudinal observational study of 60 pregnant women was undertaken in two observation periods. During the third trimester, plaque Index (PI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were assessed, and the basal levels of progesterone, CRP, IL-6 and TNF-α in plasma were measured. The second observation phase was carried out 6 weeks after childbirth, when periodontal indices, progesterone and serum levels of CRP were again evaluated. Results: Periodontal disease was moderate in 18.3%. PI and toothbrushing proved to have a correlation with the severity of periodontitis. High levels of CRP were significantly correlated (p 0.05), with a greater BOP (r = 0.360) and PPD (r = 0.321). There was no correlation between IL-6 or TNF-α with periodontal parameters. After childbirth, progesterone was drastically reduced, BOP and PPD improved and CRP showed a significant reduction of 2.63 mg/l (p 0.05). Conclusions: Periodontal disease is prevalent during pregnancy. PI and frequency of toothbrushing are correlated with the severity of periodontitis in pregnant women. Pregnancy showed an increased in the level of CRP, which was positively correlated with BOP and PPD. All periodontal indices and CRP level statistically significantly decreased after childbirth, together with a marked reduction of progesterone and without changes in PI. Keywords: anti-inflammatory agents, gynecology, periodontitis, pregnancy, obstetrics