To investigate the correlation of levels of procalcitonin (PCT) and blood lactic acid with the effectiveness of the non-invasive ventilation (NIV) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with different severities. We used a case-control method to study patients who were admitted for AECOPD to the ICU at the Second Affiliated Hospital of Soochow University from January 1, 2012, to December 31, 2014. The patients had shown no response to conventional therapy or NIV treatment. The patients who had been treated with NIV before ICU admission were excluded. According to the pH value of arterial blood gas analysis after ICU admission, the AECOPD patients were divided into a mild group (pH ≥ 7.30) and a severe group (pH < 7.30). On the basis of whether a patient needed an artificial airway after NIV therapy, the two groups of patients were divided into two subgroups: an effective group and an ineffective group. A total of 153 patients were screened for the study. Of the 62 patients in the mild group, 38 cases were in the effective group, while 24 cases were in the ineffective group. Through the comparative analysis of clinical features of the patients in the two subgroups before NIV therapy, the single factor analysis between groups was applied to find the factor that influenced the effectiveness of NIV in the treatment of AECOPD with different severities. The logistic regression for multi-factor analysis was applied. The results implied that the level of procalcitonin (PCT) in patients of the effective group was significantly lower than the level in the ineffective group (0.95 ± 0.54 vs. 1.34 ± 0.70, p = 0.016). Of 89 patients in the severe group, 33 cases were in the effective group, while 56 cases were in the ineffective group. The results indicated that levels of PCT (0.99 ± 0.57 vs. 1.46 ± 0.81, p = 0.004) and blood lactic acid (1.5 ± 0.5 vs. 1.9 ± 0.8, p = 0.008) in patients of the effective group were significantly lower than levels of the ineffective group. The PCT and blood lactic acid, which reflect the infection severity, are factors influenced by the effectiveness of NIV in the treatment of AECOPD of different severities.