Isolation is the theme of this story, as indicated from the first two lines:

There were only two Americans stopping at the hotel. They did not know any of the people they passed on the stairs on their way to and from their room.

More significantly, the unnamed husband and wife are isolated and alienated from each other. They don't seem well suited as a couple. The husband likes to read and is absorbed in his interior life. The wife lives externally, concerned with the outer world: her hair, her clothes, rescuing a kitty from the rain. She seems supremely dissatisfied with her life and seems to have the mistaken idea that if she changes her outer circumstances, her inner life will repair:

And I want to eat at a table with my own silver and I want candles. And I want it to be spring and I want to brush my hair out in front of a mirror and I want a kitty and I want some new clothes.

Both people in this relationship are wounded, members of the alienated Lost Generation that arose after World War I, unmoored from traditional values because of the horror of that carnage. The war becomes a part of their story through the nearby war monument that many Italians like to visit, presumably to mourn their losses. The two Americans each deal with their woundedness differently: the man withdraws into his book and becomes emotionally indifferent to his wife, while his withdrawal causes her to become more demanding.

The wife tries to deal with her inner emptiness by rescuing the wet cat outside in the way she would like to be rescued from her own predicament. She fails to connect with the cat, but as the story draws to a close, one of the Italian hotel workers brings her a different cat. The story ends with a thud of hopelessness: it is evident this cat is not going to fill the lonely hole in the wife's heart.

Hemingway uses short, spare words and brief dialogue to underscore the alienation and isolation the couple feels. He never intrudes with an omniscient narrator who tells us what the couple is experiencing but simply lets us realize it by showing us what is going on.

The theme of isolation is a common one in Hemingway's fiction, and it's very much on display in “Cat in the Rain.” It's typically the case that isolated characters in Hemingway are often surrounded by people or in close proximity to family members or lovers. Though they have people around them, they are still emotionally estranged from them for one reason or another.

That's certainly the case with the unnamed American wife in “Cat in the Rain”. She feels so isolated, despite the presence of her husband in the same hotel bedroom, that she ventures out into the pouring rain to fetch a cat that's trying to keep dry. The wife needs companionship, something that's being denied to her by a self-absorbed husband who doesn't take her needs into account. Hence the importance she attaches to saving the cat from the rain.

In the cat, the wife detects a kindred spirit—a creature that needs warmth, love, and attention; all the things that she's being denied by an indifferent, self-centered husband. Already feeling isolated by her husband, the rain, and staying in a foreign country, the wife desperately needs something to make her feel a connection with the world around her. At this precise moment in time, only the cat in the rain can do that.

The theme of Hemingway's short story "Cat in the Rain" is isolation, public and personal isolation. George and his unnamed "American wide," also called "American girl" by the narrator, come to vacation in Italy near the sea, by a "public garden," and by a "war monument."

The narrator makes the point that Italians come from great distances to see the war monument and that artists like to paint and draw it; yet George and his "American wife" seem almost stationary in their hotel room. Granted, it is raining, but the contrast to the Italians and the stasis with which Hemingway opens and closes the story, with George unmoved and in the same position, gives a sense of permanency to their indifference and isolation from public gardens, war memorials, and refreshing sea breezes.

It is this mood of stasis that represents public isolation: George and the girl are not involved in the activities of public living. Even the hotel owner acts on the wife's behalf by sending a maid after her with an umbrella when she fails to be involved enough to ask for one on her own behalf.

Their personal isolation is best illustrated after the wife comes back in from trying to rescue the kitty in the rain (symbolically representative of the "American wife" herself). She starts talking about wanting the kitty and other tangibles since she can't have any fun, which is symbolically representative of happiness:

"Anyway, I want a cat," she said, "I want a cat. I want a cat now. If I can't have long hair or any fun, I can have a cat."

The narrator makes the point that George "hadn't looked away from her since she started to speak," saying, "You look pretty darn nice to me." This is the pivotal line of the short story, the line that points out the theme. She is so isolated that she can't recognize George's overtures of emotional intimacy, i.e., undivided attention and admiration. Once she resumes her litany of desire for the kitty and for material objects that replace involvement, he shows himself to be so equally isolated that instead of exerting himself to break through their isolation, he turns away and resumes reading a book, advising her to do the same: "Oh, shut up and get something to read."