We introduce a concept of blown-up Čech cohomology for coherent sheaves of homological dimension ≤ 1 and some quasi-coherent sheaves on a non-singular real affine variety. Its construction involves a directed set of multi-blowups. We establish, in particular, long exact cohomology sequence and Cartan's Theorem B. Finally, some applications are provided, including universal solution to the first Cousin problem (after blowing up).2010 Mathematics Subject Classification. Primary 14P05, 14F05, 13D05.