Besides Mycoplasma hyopneumoniae (M. hyopneumoniae), many other viruses and bacteria can concurrently be present in pigs. These pathogens can provoke clinical signs, known as porcine respiratory disease complex (PRDC). A sampling technique on live animals, namely tracheobronchial swab (TBS) sampling, was applied to detect different PRDC pathogens in pigs using PCR. The objective was to determine prevalence of different PRDC pathogens and their variations during different seasons, including correlations with local weather conditions. A total of 974 pig farms and 22,266 pigs were sampled using TBS over a 5-year period. TBS samples were analyzed using mPCR and results were categorized and analyzed according to the season of sampling and local weather data. In samples of peri-weaned and post-weaned piglets, influenza A virus in swine (IAV-S), porcine reproductive and respiratory syndrome virus-European strain (PRRSV1), and M. hyopneumoniae were found as predominant pathogens. In fattening pigs, M. hyopneumoniae, porcine circovirus type 2 (PCV-2) and PRRSV1 were predominant pathogens. Pathogen prevalence in post-weaned and finishing pigs was highest during winter, except for IAV-S and A. pleuropneumoniae, which were more prevalent during autumn. Associations between prevalence of several PRDC pathogens, i.e., M. hyopneumoniae, PCV-2 and PRRSV, and specific weather conditions could be demonstrated. In conclusion, the present study showed that many respiratory pathogens are present during the peri-weaning, post-weaning, and fattening periods, which may complicate the clinical picture of respiratory diseases. Interactions between PRDC pathogens and local weather conditions over the 5-year study period were demonstrated.