Severe inflammation is a hallmark of viral disease including COVID-19. The cellular source of the initial and ongoing inflammation in COVID-19 is unknown. Macrophages, as sentinel innate immune cells, are specialised for detecting infection and releasing potent pro-inflammatory (IL-6, TNF, IL-1b) and anti-viral cytokines (e.g. IFNb). They are recruited to the lung in large numbers during severe COVID-19. However, whether these macrophages are directly infected with SARS-CoV-2 and whether they are the source of pathogenic inflammation is unclear. Primary human monocyte derived macrophages (HMDM) are a suitable in vitro model for investigating human macrophage inflammatory responses to viral infection. HMDM did not support SARS-CoV-2 replication, as determined by viral RNA accumulation and plaque assay at MOI 5 or MOI 0.5. In contrast, pandemic H1N1 (pH1N1) 2009 Influenza A Virus (IAV) infected and replicated in HMDM. While IAV induced strong pro-inflammatory (IL-6, TNF, IL-1b) and anti-viral (IFNb, CXCL10) responses over time, indicative of detection of replicating viral RNA, SARS-CoV-2 only induced macrophage pro-inflammatory and anti-viral responses at MOI 5. Therefore, HMDM sense incoming SARS-CoV-2 virions to trigger inflammation, unlike IAV where both incoming virions and replicating virus are sensed. Blocking macrophage specific sensing pathways to block inflammation may prevent pathologic inflammation in severe COVID-19 and IAV infections.