Multiplex PCR panels have been used for the diagnosis of viral respiratory infections in the last years. While the types of manufacturer validated and thus officially approved materials are usually limited, the tested materials in the clinical routine or studies often vary, which presents a challenge in light of the new EU-IVDR guideline. Aim of our present study was to evaluate if testing of lower respiratory tract (LRT) or saline gargle specimens (SGS) provided an advantage compared to the testing of nasopharyngeal swabs (NPS) and if the testing of pleural effusions (PE) provided any advantage compared to the testing of LRT samples. We included 367 NPS vs LRT cases, of which 202 (55%) were negative in both samples, 108 (29%) were positive in both samples, 28 (8%) had a positive NPS and a negative LRT and 29 (8%) had a negative NPS but a positive LRT, with no significant differences between immunocompetent and immunosuppressed cases. We included 46 NPS vs SGS cases, of which 18 (39%) were negative in both samples, 18 (39%) were positive in both samples, 4 (9%) had a positive NPS and a negative SGS and 6 (13%) had a negative NPS but a positive SGS. Out of the 82 tested PE samples, only one (1%) was positive for Influenza B RNA (detected in the PE but not LTR), while for 5 positive LTR samples no viral genome could be detected in the PE. The samples were tested with the FTD respiratory viral panel for common respiratory viruses. Testing of a lower respiratory tract sample after a negative upper respiratory tract sample may have an incremental diagnostic value. Gargle and nasopharyngeal swab samples seem to have a comparable diagnostic performance, while pleural effusion is a substandard material for the diagnosis of common respiratory virus infections.