If you're talking about physical comfort:
* Incómodo/a: This is the most direct opposite, meaning uncomfortable.
* Desagradable: This implies something unpleasant or disagreeable.
* Estrecho/a: This means narrow or cramped.
* Duro/a: This means hard or stiff.
If you're talking about feeling comfortable in a situation:
* Inseguro/a: This means insecure or uneasy.
* Tímido/a: This means shy or timid.
* Desconfiado/a: This means distrustful or suspicious.
* Preocupado/a: This means worried or concerned.
Examples:
* "El sofá es muy cómodo." (The sofa is very comfortable.)
* "El sofá es muy incómodo." (The sofa is very uncomfortable.)
* "Me siento incómodo en esta situación." (I feel uncomfortable in this situation.)
* "Ella se siente insegura en la ciudad." (She feels insecure in the city.)
Ultimately, the best word to use depends on the specific situation and the nuance you want to convey.