Synoptic events may play an important role in determining the CO2 spatial distribution and temporal variations on a regional scale. In this study, we chose a front that passed the WLEF tower site on 16 August 2001, which had the most significant CO2 concentration variation in our case pool. The CO2 concentration, or 2>, at the WLEF site had a strong dip and an increasing trend before the front arrived and a decreasing trend afterward. The concentration at 396 m above the ground varied by more than 40 ppm within 36 hours. We investigated the CO2 variations associated with this frontal case using a fully coupled model of land surface physics and carbon exchange (SiB 2.5) and the atmosphere (RAMS 5.04), in which CO2 was treated as a free variable and used to determine photosynthesis rate. Our simulation showed that high-2> air mass was built up in the southern Great Plains on 14 and15 August 2001 because of the slow photosynthesis rate caused by hot and dry air over Oklahoma and Texas and the relatively strong nighttime respiration in the southeast United States. The low-2> air to the southwest of Wisconsin and the high-2> air over Kansas and Oklahoma traveled north and was responsible for part of the 2> variations at the WLEF site from 15 to 16 August 2001. Surface weather station confirmed the hot and dry weather in Oklahoma and Texas in this event, and the tower observations corroborated the existence of southwest-northeast concentration gradient. Weak daytime photosynthesis on 15 August 2001 and stronger nighttime respiration on 16 August 2001 under overcast sky condition were also partially responsible for the quick CO2 accumulation at the lower levels at the WLEF site before the front's arrival. This case study confirmed the existence of mixing signals from at least two different scales: large-scale horizontal advection and local ecosystem response to the changing weather. SiB-RAMS showed its strength in simulating the coherent anomalies in biospheric CO2 flux and in the regional weather pattern. Further refinement of the model is needed to better capture the timing and location of synoptic events and CO2 signals that travel across North America. Exploitation of continuous tower data in data assimilation and inverse modeling to determine regional sources and sinks will require careful error attribution to either transport or surface flux estimates.