1. Grid System: One key difference between Pure and Skeleton is the grid system they use. Pure utilizes a responsive 12-column grid while Skeleton uses a responsive 16-column grid. This difference in the grid system can impact how layouts are structured and how content is arranged on the website.

2. Customization Options: Pure offers less customization options compared to Skeleton. Pure is more opinionated in its design and structure, making it easier for beginners to work with but limiting the level of customization. On the other hand, Skeleton allows for more flexibility and customization, making it suitable for advanced users who want more control over their website's design.

3. Component Library: Pure comes with a set of minimalistic CSS modules focusing on basic styling elements like buttons, forms, and tables. In contrast, Skeleton provides a more comprehensive set of CSS components, including styles for navigation bars, grids, typography, and buttons. This difference in the component library can influence the overall look and feel of the website.

4. File Size: Pure has a smaller file size compared to Skeleton. This can make Pure a better choice for projects where file size optimization is crucial, as it can help improve website loading speed and performance. On the other hand, Skeleton's larger file size may offer more features and options but can impact loading times.

5. Community Support: Skeleton has a larger and more active community compared to Pure. This means that users of Skeleton may have more resources, documentation, and community support available to them when working on their projects. On the other hand, Pure's community might be smaller, leading to potentially fewer resources and support options for users.

In Summary, the key differences between Pure and Skeleton lie in their grid system, customization options, component library, file size, and community support, impacting how developers can work with each framework in building websites.