Helicobacter pylori (H. pylori) initiates a robust host immune response and subsequently results in chronic inflammation in the gastric mucosa. This study monitored the circulating monocyte subsets and measured the plasma levels of IL-10 and IL-12 in response to H. pylori infection in 35 H. pylori-associated gastritis patients and 14 healthy controls. We found that the numbers of CD14+CD163-CD64+ M1-like monocytes as well as CD14+CD163+CD206+, CD14+CD163+CD209+, and CD14+CD163+IL-10+ M2-like monocytes were significantly increased in H. pylori-infected patients in comparison with the controls, accompanied by higher levels of plasma IL-10. In addition, IL-10 production was significantly higher in the stimulated M2-like cells from patients with H. pylori infection compared with controls. Moreover, the H. pylori-infected patients with CagA- or VacA-positive strains had a significantly higher number of CD14+CD163+CD206+, CD14+CD163+CD209+, CD14+CD163+IL-10+ monocytes compared to those with CagA- or VacA-negative strains. Furthermore, patients suffering from H. pylori-positive peptic ulcers had a greater number of CD14+CD163+CD209+ monocytes than H. pylori-positive nonatrophic or atrophic gastritis patients, with the numbers of CD14+CD163+CD209+ monocytes positively correlated with the extent of H. pylori infection. Notably, the triple anti-H. pylori therapy significantly reduced the numbers of CD14+CD163+CD206+ and CD14+CD163+CD209+ monocyte subsets. In conclusion, CD14+CD163+CD209+ M2-like monocyte subsets are increased in H. pylori infection, especially in patients with peptic ulcers. CD14+CD163+CD209+ M2-like monocytes are positively associated with the severity of H. pylori infection.