Fuel moisture limits the availability of fuel to wildfires in many forest areas worldwide, but the effects of climate change on moisture constraints remain largely unknown. Here we addressed how climate affects fuel moisture in pine stands from Catalonia, NE Spain, and the potential effects of increasing climate aridity on burned area in the Pyrenees, a mesic mountainous area where fire is currently rare. We first quantified variation in fuel moisture in six sites distributed across an altitudinal gradient where the long-term mean annual temperature and precipitation vary by 6–15 °C and 395–933 mm, respectively. We observed significant spatial variation in live (78–162%) and dead (10–15%) fuel moisture across sites. The pattern of variation was negatively linked (r = |0.6|–|0.9|) to increases in vapor pressure deficit (VPD) and in the Aridity Index. Using seasonal fire records over 2006–2020, we observed that summer burned area in the Mediterranean forests of Northeast Spain and Southern France was strongly dependent on VPD (r = 0.93), the major driver (and predictor) of dead fuel moisture content (DFMC) at our sites. Based on the difference between VPD thresholds associated with large wildfire seasons in the Mediterranean (3.6 kPa) and the maximum VPD observed in surrounding Pyrenean mountains (3.1 kPa), we quantified the “safety margin” for Pyrenean forests (difference between actual VPD and that associated with large wildfires) at 0.5 kPa. The effects of live fuel moisture content (LFMC) on burned area were not significant under current conditions, a situation that may change with projected increases in climate aridity. Overall, our results indicate that DFMC in currently fire-free areas in Europe, like the Pyrenees, with vast amounts of fuel in many forest stands, may reach critical dryness thresholds beyond the safety margin and experience large wildfires after only mild increases in VPD, although LFMC can modulate the response.