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Abstract Understanding the seasonality of respiratory syncytial virus (RSV) is crucial for cost-effective seasonal RSV prophylaxis administration. The impact of short-term changes in air pollution and meteorological factors on RSV epidemics, particularly their spatial variations, remains unclear. We conducted a time-series analysis to investigate the association between short-term environmental changes and weekly RSV infection in Chile. Weekly data on the number of new laboratory RSV tests and confirmed RSV-positive cases, meteorological factors, and air pollutants were collected from 16 Chilean regions (2015–2018). We fitted a quasi-Poisson regression to evaluate the link between short-term environmental changes and RSV infection in each region. We utilized random effects meta-analyses to pool the region-specific estimates. Subgroup analyses were further conducted to assess variations by socio-economic and geographical context. Nationwide associations were observed between weekly average temperature and RSV activity, with a 1 °C increase being positively associated with an 8.2% (95% confidence interval: 0.87–0.97) decrease in RSV positivity at a lag of 3 weeks. In addition, we found significant positive nationwide associations between air pollutants, i.e., nitrogen dioxide ( $${{\rm{NO}}}_{2}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mrow> <mml:mi>NO</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>2</mml:mn> </mml:mrow> </mml:msub> </mml:math> ) and particulate matter smaller than 2.5 μm ( $${{\rm{PM}}}_{2.5}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mrow> <mml:mi>PM</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>2.5</mml:mn> </mml:mrow> </mml:msub> </mml:math> ), and RSV activity. A 5- $${\rm{\mu }}{\rm{g}}/{{\rm{m}}}^{3}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mrow> <mml:mi>μ</mml:mi> <mml:mi>g</mml:mi> </mml:mrow> <mml:mo>/</mml:mo> <mml:mrow> <mml:msup> <mml:mrow> <mml:mi>m</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>3</mml:mn> </mml:mrow> </mml:msup> </mml:mrow> </mml:mrow> </mml:math> increase in $${{\rm{PM}}}_{2.5}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mrow> <mml:mi>PM</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>2.5</mml:mn> </mml:mrow> </mml:msub> </mml:math> and $${{\rm{NO}}}_{2}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mrow> <mml:mi>NO</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>2</mml:mn> </mml:mrow> </mml:msub> </mml:math> concentrations was positively associated with an increase in RSV positivity of 3.4% (1.00–1.06) and 10.2% (1.05–1.15) at lags of 3 weeks, respectively. We also observed regional variations of environmental impacts on RSV activity across Chile, including $${{\rm{PM}}}_{2.5}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mrow> <mml:mi>PM</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>2.5</mml:mn> </mml:mrow> </mml:msub> </mml:math> and particulate matter smaller than 10 micrometers ( $${{\rm{PM}}}_{10}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mrow> <mml:mi>PM</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>10</mml:mn> </mml:mrow> </mml:msub> </mml:math> ). The study suggests that improving air quality could potentially lower the RSV activity, especially in highly polluted areas. Furthermore, temperature and air quality changes may be used for predicting short-term shifts in RSV activity, informing RSV prevention efforts.