Abstract: Pneumonia is a highly incident acute respiratory infection worldwide, and Inula britannica displayed an anti-pneumonia effect. Herein, twenty compounds, including seven newly discovered compounds six terpenoids inulabritanoids P-U (1−6) and one novel lignan inulabritanoid V (7) and thirteen known compounds (8−20), were obtained from I. britannica and its framework structure were clarified through 1D and 2D NMR, and HR-MS data. Effects of all the elucidated compounds for anti-pneumonia activities were assessed using the lipopolysaccharide (LPS)-induced pneumonia model in MH-S alveolar macrophages. Compounds 3, 5, 6, 12, and 18 showed potent anti-pneumonia activities in LPS-exposed MH-S cells. Notably, compound 6 exhibited the most potent bioactivity: it significantly inhibited nitric oxide (NO) production and downregulated expression levels of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), IL-6, and chemokine (C-C motif) ligand 5 (CCL5). Further investigations revealed that the anti-pneumonia effect of compound 6 depended on inhibiting the NF-κB and MAPK/AP-1 signaling pathways. These results illustrated that compound 6 served as a viable lead molecule for combating pneumonia, laying a foundation for future studies.