Dysbiosis of the sinus microbiome affects the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNPs). We investigated whether the sinus microbiota in CRSwNPs is associated with eosinophilic inflammation, especially in relation to innate lymphoid cells (ILCs), prognosis, and serum extracellular vesicles (EVs). Middle meatal swabs and serum from 31 CRSwNPs patients and six healthy controls were analyzed by 16S ribosomal RNA sequencing. ILC2s and cytokines from sinonasal tissues were measured by flow cytometry and ELISA, respectively. The relative abundances (RAs) of bacteria were compared based on eosinophilic inflammation and surgical outcome. The correlations between sinus bacteria and ILC2s, cytokines, and serum EVs were analyzed. The compositions of sinus bacteria were different between groups at the genus level. In eosinophilic CRSwNPs patients, the RA of
Anaerococcus
was significantly decreased (
P
= 0.010), whereas that of
Lachnoclostridium
was significantly increased (
P
= 0.038) compared with that in controls. The RA of
Lachnoclostridium
showed a significant positive correlation with interleukin (IL)-5-producing ILC2 populations (
R
= 0.340,
P
= 0.049), whereas the RA of
Anaerococcus
showed a negative correlation with IL-5-producing ILC2 populations (
R
= −0.332,
P
= 0.055). The RAs of
Corynebacterium
,
Anaerococcus
, and
Tepidimonas
were significantly decreased in patients with suboptimal outcomes compared with those in patients with optimal outcomes and control subjects. Some sinus bacteria and serum EVs showed positive correlations. CRSwNPs patients showed distinct microbiota compositions based on eosinophilic inflammation in relation to ILC2s and surgical outcome. These findings support a relationship between the microbiota and the host immune response in CRSwNPs.