Abstract: Objective To analyze the epidemiological characteristics of 8 major respiratory pathogens in influenza-like illness (ILI) cases among acute respiratory infections at fever clinics in Shanghai from 2015 to 2024, providing scientific data for proper prevention and treatment of respiratory diseases. Methods A retrospective study was conducted in Huangpu District from 2015 to 2024, with enrolled individuals meeting the case definition of influenza-like illness. Their nasopharyngeal swabs were collected and tested. A total of 8 respiratory viruses were tested, including Influenza A virus (Flu A), Influenza B virus (Flu B), adenovirus (ADV), enterovirus/human rhinovirus (EV/HRV), human parainfluenza virus (HPIV), human coronaviruses(HCoV), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV). Results From 2015 to 2019, a total of 344 cases were sampled for ILI, of which 192 cases (55.81%) were tested positive for single respiratory pathogen. From 2023 to 2024, a total of 1557 cases were sampled for ILI, with 572 (36.74%) cases being positive for single pathogen. From 2023 to 2024, the positive rate of single pathogen in ILI cases at fever clinics showed a decline compared to the period from 2015 to 2019 (χ²=42.66, P<0.001), while the positive rate of both Flu A (χ²=74.43，P<0.001) and HPIV (χ²=8.66, P=0.003) showed a significantly difference.According to the seasonal pattern, the epidemic of Flu A decreased in summer, while the prevalence of HPIV increased in summer and autumn. Demographic results showed statistically significant differences in the -positive rates of EV/HRV between genders (χ² = 22.38, P < 0.001), with males exhibiting a higher positive detection rate than females. No statistically significant differences were identified in the positive rates of single pathogen among different age groups (χ² = 4.42, P = 0.110). Nevertheless, statistically significant differences were noted when comparing the positive rates of EV/HRV, Flu A, Flu B and HPIV across different age groups (P < 0.05). EV/HRV was more commonly detected in the 15~24 age group (10.93%), while Flu A and HPIV had the highest positive rates in the ≥60 age group (21.24% and 4.77%). Flu B had the highest positive rate in the 25~59 age group (11.26%). 52.63% of cases of co-infection occurred during winter, with the primary pathogens involved being EV/HRV (9 cases) and HCoV (6 cases). The most prevalent combination of co-infection was Flu A and EV/HRV. Conclusions The prevalence of respiratory pathogens among ILI patients from 2023 to 2024 exhibited notable fluctuations compared to that from 2015 to 2019. Therefore ILI surveillance should be strengthened, and besides influenza, attention should also be paid to the prevalence of respiratory pathogens such as human parainfluenza viruses. These findings have profound implications for future studies, surveillance, vaccine planning, and public health policy making.