Disease course in Idiopathic Pulmonary Fibrosis (IPF) is highly heterogeneous and markers of disease progression would be helpful. Blood leukocyte count has been studied in cancer patients and a reduced lymphocyte to monocyte ratio (LMR) has been show to predict survival. Thus, we aimed to investigate the role of monocytes count and LMR in three distinct population of patients with IPF: 77 newly-diagnosed IPF, 40 with end-stage IPF and 17 IPF with lung cancer. In newly-diagnosed IPF patients, we observed a negative correlation between forced vital capacity (FVC) at diagnosis and both white blood cells and monocytes count (r = −0.24; p = 0.04 and r = −0.27; p = 0.01; respectively). Moreover, a high monocytes count was independently associated with functional decline (OR: 1.004, 95%CI 1.00–1.01; p = 0.03). In newly-diagnosed IPF, the LMR cut-off at diagnosis was 4.18 with an AUC of 0.67 (95%CI 0.5417–0.7960; p = 0.025), and overall survival was significantly worse in patients with a LMR<4.18 compared to patients with a LMR≥4.18 (HR: 6.88, 95%CI 2.55–18.5; p = 0.027). LMR was significantly lower in IPF patients with lung cancer compared to those newly diagnosed with IPF [2.2 (0.8–4.4), 3.5 (0.8–8.8); p < 0.0001] and those with end-stage disease [3.6 (2–6.5); p < 0.0001]. In conclusion, a LMR<4.18 is associated with significantly shorter survival in newly-diagnosed IPF patients. In addition, LMR is significantly lower in patients with IPF and lung cancer compared to patients with newly-diagnosed IPF. High monocytes count at baseline negatively correlates with FVC and is an independent predictor of disease progression in newly-diagnosed IPF patients.