Serpentine, multi-pass cooling passages are used in cooling advanced gas turbine blades. In the open literature, most internal cooling studies use a fixed cross-sectional area for multi-pass channels. Studies that use varying aspect ratio channels, along with a guide vane to direct the flow with turning, are scarce. Therefore, this study investigates the effect of using different guide vane designs on both detailed heat transfer distribution and pressure loss in a multi-pass channel with an aspect ratio of (4:1) in the entry passage and (2:1) in the second passage downstream of the vane(s). The first vane configuration is one solid vane with a semi-circular cross section connecting the two flow passages. The second configuration has three broken vanes with a quarter-circular cross section; two broken vanes are located downstream in the first passage, and one broken vane is upstream in the second passage. Detailed heat transfer distributions were obtained on all surfaces within the flow passages by using a transient liquid crystal method. Results show that including the semi-circular vane in the turning region enhanced the overall heat transfer by around 29% with a reduction in pressure loss by around 20%. Moreover, results show that the quarter-circular vane design provides higher overall averaged heat transfer enhancement than the semi-circular vane design by around 9% with penalty of higher pressure drop by 6%, which yields higher thermal performance by 7%, over a Reynolds number range from 15,000 to 45,000.