The synthesis of thermoresponsive graft copolymers based on a carboxymethylcellulose (CMC) backbone is reported. Thermal responsive properties are introduced by grafting the CMC sample with amino-terminated poly(N-isopropylacrylamide) (PNIPAM) side chains of a relatively low molecular weight. Turbidity measurements in dilute copolymer solutions showed that, due to the hydrophilic CMC backbone, macroscopic phase separation by increasing temperature above the lower critical solution temperature (LCST) of PNIPAM is not allowed for pH greater than or equal to 3. Pyrene fluorescence probing studies in aqueous solutions revealed the formation of hydrophobic microdomains above the LCST of PNIPAM. In semidilute solution these microdomains interconnect the polymer chains, leading to the thermally induced formation of a physical network. The macroscopic result is the observation in semidilute solutions of a pronounced thermally induced viscosity enhancement. This thermothickening phenomenon is almost irrespective of pH, and it remains very important even at pH values as low as 3.