Background To detect the serum antibodies against respiratory viruses and atypical pathogens in adults with community-acquired pneumonia (CAP) in Guangzhou City (Guangdong province, China). Methods A retrospective study was carried out with samples from 685 adults who were admitted with CAP and 108 non-CAP control patients. Atypical pathogens and respiratory viruses in serum were detected using the Pneumoslide IgM test from Vircell, Spain. All patients were divided into 6 groups according to age: 18-24, 25-44, 45-59, 60-74, 75-89, and >90. Results The total positive rate of CAP was 35.4%, which was highest in the 18-24 age group (P < .05). The highest positive rate, 17.11%, was observed forMycoplasma pneumoniae(MP). The mean age of MP-infected patients was higher than that of the controls (P < .05). The positive rates forinfluenza B(INFB),Legionella pneumophila(LP1),Coxiella burnetii(COX), influenza A (INFA), parainfluenza virus (PIV), respiratory syncytial virus (RSV),Chlamydophila pneumoniae(CP), and adenovirus (ADV) were 5.56%, 3.07%, 2.63%, 2.34%, 1.90%, 1.61, 0.88%, and 0.29%, respectively. There were 4.37% of patients with CAP having multiple infections. The main symptoms observed in the 685 CAP patients were cough and sputum production, in 78.4% and 67.4%. Fever was followed by 54% of CAP patients. Dyspnea (39.1%), anorexia (36.8%), increased thirst (26.7%), chills (18.7), headache (14.6%), and nausea (13.1%) were also frequently observed in the CAP patients. Conclusions MP infection was the most common in adult CAP patients in Guangzhou City with the highest positive rate in the 18-24 age groups.